IP Library › Granted Patent US 12,734,238
Granted Patent B2
US 12,734,238 · App. 17/902,814 · Granted Sep 15, 2026

Cancer treatment methods using thermotherapy and/or enhanced immunotherapy

Inventor: Gholam A. Peyman (Sun City, AZ)
A61K41/0033A61K9/127A61K31/337A61K39/0011A61K41/0052A61K49/225A61N7/02
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,734,238
App. No.
17/902,814
Granted
Sep 15, 2026
Kind
B2
Abstract

Cancer treatment methods using thermotherapy and/or enhanced immunotherapy are disclosed herein. In one embodiment, the method comprising the steps of: (i) applying controlled thermal energy at 40-43° C. for a first predetermined time period to damage and weaken tumor cells of a tumor in a patient; (ii) administering pulsed high intensity focused ultrasound (pHIFU) in a first ultrasound mode to the tumor cells in the patient so as to damage the tumor cells without increasing the thermal energy; and (iii) administering low intensity focused ultrasound (LIFU) in a second ultrasound mode to further damage the tumor cells at a temperature of 39-43° C. for a second predetermined time period while performing observation of the tumor cells by ultrasonic thermometry.

Claims (25)

1 . A cancer treatment and imaging method comprising the steps of:

systemically administering antibody-coated piezoelectric nanoparticles to a patient in need thereof so as to target a tumor in the patient, the piezoelectric nanoparticles being further coated with a biocompatible polymer, and a medication being conjugated with the biocompatible polymer coating of the piezoelectric nanoparticles, the piezoelectric nanoparticles attaching to surface antigens of tumor cells of the tumor so as to accumulate at a site of the tumor and form a tumor cell/nanoparticle complex;

applying a pulsed electrical current to the piezoelectric nanoparticles using an electrical source at the site of the tumor so as to create an electroacoustic sound from the piezoelectric nanoparticles, the electrical source comprising a power generation device with an anode located on a first side of the skin of the body of the patient and a cathode being located on a second side of the skin of the body of the patient, the anode being located on a first side of the tumor and the cathode being located on a second side of the tumor, and the piezoelectric nanoparticles accumulated at the site of the tumor generating the electroacoustic sound in response to the pulsed electrical current applied to the piezoelectric nanoparticles, the pulsed electrical current passing through the tumor in the body of the patient from the first side of the tumor to the second side of the tumor;

recording the electroacoustic sound generated by the piezoelectric nanoparticles using a transducer to convert the electroacoustic sound to an electrical signal; and

amplifying and transmitting the electrical signal to a processor so that a 1-dimensional, 2-dimensional, or 3-dimensional image of the tumor structure is able to be generated in the form of an electroacoustic computed tomogram.

2 . The cancer treatment and imaging method according to claim 1 , wherein the method further comprises the step of:

increasing the permeability of one or more tumor cell membranes of the tumor using the pulsed electrical current or a thermal energy source, thereby facilitating the entry of the medication into the tumor cells of the tumor.

3 . The cancer treatment and imaging method according to claim 1 , wherein the method further comprises the step of:

heating the piezoelectric nanoparticles using a high power focused ultrasound source operating in a thermal mode so as to raise the temperature of the tumor cell/nanoparticle complex to a temperature of between 40° C. and 45° C., thereby damaging one or more tumor cell membranes at the tumor site and melting the biocompatible polymer coating of the nanoparticles to release the medication at the tumor site.

4 . The cancer treatment and imaging method according to claim 3 , where the power generation device of the electrical source comprises a battery device, the pulsed electrical current passing through the body of the patient from the anode to the cathode of the battery device, and where the pulsed electrical current further damages the one or more tumor cell membranes at the tumor site and drives the released medication into the tumor cells at the tumor site.

5 . The cancer treatment and imaging method according to claim 1 , wherein the method further comprises the steps of:

administering antibody-coated magnetic or paramagnetic nanoparticles to the patient; and

exciting the magnetic or paramagnetic nanoparticles using an energy source producing an alternating magnetic field operating in a thermal mode so as to raise the temperature of the tumor cell/nanoparticle complex to a temperature of between 40° C. and 45° C., thereby damaging one or more tumor cell membranes at the tumor site and melting the biocompatible polymer coating of the nanoparticles to release the medication at the tumor site.

6 . The cancer treatment and imaging method according to claim 5 , wherein the alternating magnetic field operating in the thermal mode has a frequency greater than 300 kilohertz.

7 . The cancer treatment and imaging method according to claim 1 , wherein the piezoelectric nanoparticles are selected from the group consisting of quartz nanoparticles, perovskite nanoparticles, zinc oxide nanoparticles, and combinations thereof.

8 . A cancer treatment and imaging method comprising the steps of:

systemically administering antibody-coated pyroelectric nanoparticles to a patient in need thereof so as to target a tumor in the patient, the pyroelectric nanoparticles being further coated with a biocompatible polymer, and a medication being conjugated with the biocompatible polymer coating of the pyroelectric nanoparticles, the pyroelectric nanoparticles attaching to surface antigens of tumor cells of the tumor so as to accumulate at a site of the tumor and form a tumor cell/nanoparticle complex;

applying a pulsed electrical current to the pyroelectric nanoparticles using an electrical source at the site of the tumor so as to create an electroacoustic sound from the pyroelectric nanoparticles, the electrical source comprising a power generation device with an anode located on a first side of the skin of the body of the patient and a cathode being located on a second side of the skin of the body of the patient, the anode being located on a first side of the tumor and the cathode being located on a second side of the tumor, and the pyroelectric nanoparticles accumulated at the site of the tumor generating the electroacoustic sound in response to the pulsed electrical current applied to the pyroelectric nanoparticles, the pulsed electrical current passing through the tumor in the body of the patient from the first side of the tumor to the second side of the tumor;

recording the electroacoustic sound generated by the pyroelectric nanoparticles using a transducer to convert the electroacoustic sound to an electrical signal; and

amplifying and transmitting the electrical signal to a processor so that a 1-dimensional, 2-dimensional, or 3-dimensional image of the tumor structure is able to be generated in the form of an electroacoustic computed tomogram.

9 . The cancer treatment and imaging method according to claim 8 , wherein the method further comprises the step of:

increasing the permeability of one or more tumor cell membranes of the tumor using the pulsed electrical current or a thermal energy source, thereby facilitating the entry of the medication into the tumor cells of the tumor.

10 . The cancer treatment and imaging method according to claim 8 , wherein the method further comprises the step of:

heating the pyroelectric nanoparticles using a high power focused ultrasound source operating in a thermal mode so as to raise the temperature of the tumor cell/nanoparticle complex to a temperature of between 40° C. and 45° C., thereby damaging one or more tumor cell membranes at the tumor site and melting the biocompatible polymer coating of the nanoparticles to release the medication at the tumor site.

11 . The cancer treatment and imaging method according to claim 10 , where the power generation device of the electrical source comprises a battery device, the pulsed electrical current passing through the body of the patient from the anode to the cathode of the battery device, and where the pulsed electrical current further damages the one or more tumor cell membranes at the tumor site and drives the released medication into the tumor cells at the tumor site.

Continuity (8)
Continuation In Part 16200195 · Nov 26, 2018
Continuation In Part PCTUS2018054880 · Oct 8, 2018
Continuation In Part 14976321 · Dec 21, 2015
Provisional Application 62720258 · Aug 21, 2018
Provisional Application 62614456 · Jan 7, 2018
Provisional Application 62577485 · Oct 26, 2017
Provisional Application 62569592 · Oct 8, 2017
Related Publication 20230000981A1 · Jan 5, 2023
References Cited (195)
US 3993754A · Rahman et al. · 1976 [cited by applicant]
US 4235871A · Papahadjopoulos et al. · 1980 [cited by applicant]
US 4522803A · Lenk et al. · 1985 [cited by applicant]
US 4586512A · Do-huu et al. · 1986 [cited by applicant]
US 4620546A · Aida et al. · 1986 [cited by applicant]
US 4658828A · Dory · 1987 [cited by applicant]
US 4891043A · Zeimer et al. · 1990 [cited by applicant]
US 5094854A · Ogawa et al. · 1992 [cited by applicant]
US 5118666A · Habener · 1992 [cited by applicant]
US 5149319A · Unger · 1992 [cited by applicant]
US 5203782A · Gudov et al. · 1993 [cited by applicant]
US 5220181A · Kanal et al. · 1993 [cited by applicant]
US 5545618A · Buckley et al. · 1996 [cited by applicant]
US 5935942A · Zeimer · 1999 [cited by applicant]
US 5976502A · Khoobehi et al. · 1999 [cited by applicant]
US 6179767B1 · Ziegler et al. · 2001 [cited by applicant]
US 6197022B1 · Baker · 2001 [cited by applicant]
US 6248727B1 · Zeimer · 2001 [cited by applicant]
US 6552053B2 · Sun et al. · 2003 [cited by applicant]
US 6566595B2 · Suzuki et al. · 2003 [cited by applicant]
US 6583111B1 · DiMarchi et al. · 2003 [cited by applicant]
US 6641553B1 · Chee et al. · 2003 [cited by applicant]
US 6984655B1 · Mori et al. · 2006 [cited by applicant]
US 7638139B2 · Peyman · 2009 [cited by applicant]
US 8324344B2 · Kisiel · 2012 [cited by applicant]
US 8481082B2 · Peyman · 2013 [cited by applicant]
US 8808268B2 · Peyman · 2014 [cited by applicant]
US 10136820B2 · Peyman · 2018 [cited by applicant]
US 11433260B2 · Peyman · 2022 [cited by applicant]
US 20020174743A1 · Mukherjee et al. · 2002 [cited by applicant]
US 20030014089A1 · Chow et al. · 2003 [cited by applicant]
US 20030022374A1 · Greenbaum et al. · 2003 [cited by applicant]
US 20030119033A1 · Mikolajczyk et al. · 2003 [cited by applicant]
US 20040003839A1 · Curtain · 2004 [cited by applicant]
US 20050004625A1 · Chow · 2005 [cited by applicant]
US 20060173362A1 · Toms et al. · 2006 [cited by applicant]
US 20070048383A1 · Helmus · 2007 [cited by examiner]
US 20080260745A1 · Ponniah et al. · 2008 [cited by applicant]
US 20090031814A1 · Takiguchi · 2009 [cited by examiner]
US 20090156932A1 · Zharov · 2009 [cited by applicant]
US 20100185260A1 · Olson · 2010 [cited by applicant]
US 20100211146A1 · Strowbridge et al. · 2010 [cited by applicant]
US 20100303716A1 · Jin et al. · 2010 [cited by applicant]
US 20110270153A1 · Olson · 2011 [cited by applicant]
US 20110287035A1 · Peyman · 2011 [cited by applicant]
US 20120203307A1 · Schroeppel · 2012 [cited by examiner]
US 20120226139A1 · Peyman · 2012 [cited by applicant]
US 20150202466A1 · Gertner · 2015 [cited by applicant]
US 20160022976A1 · Peyman · 2016 [cited by applicant]
US 20160129131A1 · Vitari et al. · 2016 [cited by applicant]
US 20160129133A1 · McCreedy et al. · 2016 [cited by applicant]
US 20160178680A1 · Ntziachristos · 2016 [cited by examiner]
US 20160186147A1 · Cady et al. · 2016 [cited by applicant]
US 20160296175A1 · Liu et al. · 2016 [cited by applicant]
US 20220096873A1 · Peyman et al. · 2022 [cited by applicant]
Genchi, G. et al. 2017. Remote Control of Cellular Functions: The Role of Smart Nanomaterials in the Medicine of the Future. Advanced Healthcare Materials. Mar. 24, 2017. 6, 1700002 (Year: 2017). [cited by examiner]
Betal, S. et al. 2016. Magneto-elasto-electroporation (MEEP): In-vitro visualization and numerical characteristics, Nature Scientific Reports. Aug. 26, 2016. 6, 32019 (Year: 2016). [cited by examiner]
Gao et al., Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients. PLoS One, vol. 9, issue 4 (2014), pp. 1-9. [cited by applicant]
Min et al. Lentivirus-Mediated sFIt-1 Gene Fragment Transfer Suppresses Retinal Neovascularization. Current Eye Research 34 (2009) 401-410. [cited by applicant]
Mulder et al. Quantum dots for multimodal molecular imaging of angiogenesis. Angiogenesis 13 (2010) 131-134. [cited by applicant]
Singerman. Combination therapy using the small interfering RNA bevasiranib. Retina 2009, Abstract Only. [cited by applicant]
Smith et al., Bioconjugated Quantum Dots for In Vivo Molecular and Cellular Imaging. Adv. Drug Deliv. Rev. 60 (2008) 1226-1240. [cited by applicant]
You et al. Incorporation of quantum dots on virus in polycationic solution. Int. J. Nanomedicine 1 (2006) 59-64. [cited by applicant]
Lee et al. The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity. Nature, 329 (1987) 642-645. [cited by applicant]
Tomczak et al. Designer polymer-quantum dot architectures. Progress in Polymer Science, 34 (2009) 393-430. [cited by applicant]
Duan and Nle. Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings. J. Am. Chem. Soc. 129 (2007) 3333-3338. [cited by applicant]
Kim and Taton. Multicomponent nanoparticles via self-assembly with cross-linked block copolymer surfactants. Langmuir, 23 (2007) 2198-2202. [cited by applicant]
Pan et al. Silica Cross-linked Micelles Loading with Silicon Nanoparticles: Preparation and Characterization. ACS Appl. Mater. Interfaces 5 (2013) 7042-7049. [cited by applicant]
Lv et al., Surface modification of quantum dots and magnetic nanoparticles with PEG-conjugated chitosan derivatives for biological applications. Chemical Papers 67 (2013) 1404-1413. [cited by applicant]
Suzuki et al. Quantum Dot FRET Biosensors that Respond to pH, to Proteolytic or Nucleolytic Cleavage, to DNA Synthesis, or to a Multiplexing Combination. J. Am. Chem. Soc. 130 (2008) 5720-5725. [cited by applicant]
Huang et al. Intermolecular and Intramolecular Quencher Based Quantum Dot Nanoprobes for Multiplexed Detection of Endonuclease Activity and Inhibition, Anal. Chem. 83 (2011) 8913-8918. [cited by applicant]
Akbarzadeh et al. Liposome: classification, preparation, and applications. Nanoscale Research Letters 8:102 (2013) 1-9. [cited by applicant]
Sander et al. CRISPR-Cas systems for editing, regulating and targeting genomes. Nature Biotechnology 32:4 (2014) 347-355. [cited by applicant]
Peyman et al. A High-Resolution 3D Ultrasonic System for Rapid Evaluation of the Anterior and Posterior Segment. Ophthalmic Surgery, Lasers & Imaging 43 (2012) 143-151. [cited by applicant]
Helfand et al. “A Genetic-Based Approach to Personalized Prostate Cancer Screening and Treatment.” Curr Opin Urol., Jan. 2015, 25(1): pp. 1-11. [cited by applicant]
Taylor et al., “Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8+ Cytolytic T Cell Responses,” Immunity, Feb. 16, 2016, vol. 44, No. 2, pp. 274-286. [cited by applicant]
Husseini el al., “Ultrasonic-Activated Micellar Drug Delivery for Cancer Treatment,” J Pharm Sci, May 27, 2008, vol. 98, No. 3, pp. 795-811. [cited by applicant]
Kong et al., “Efficacy of Liposomes and Hyperthermia in a Human Tumor Xenograft Model: Importance of Triggered Drug Release,” Cancer Research, Dec. 15, 2000, vol. 60, pp. 6950-6957. [cited by applicant]
Phenix et al., “High Intensity Focused Ultrasound Technology, Its Scope and Applications in Therapy and Drug Delivery,” Journal of Pharmacy & Pharmaceutical Sciences, Mar. 31, 2014, vol. 17, No. 1, pp. 136-153. [cited by applicant]
PCT Form 210, International Search Report for PCT/US2018/054880, mailed on Jan. 9, 2019. [cited by applicant]
PCT Form 237, Written Opinion of the International Searching Authority for PCT/US2018/054880, mailed on Jan. 9, 2019. [cited by applicant]
E. Shaswary, Y. Xu, J. Tavakkoli, Performance study of a new time-delay estimation algorithm in ultrasonic echo signals and ultrasound elastography, Ultrasonics. 69 (2016), pp. 11-18. [cited by applicant]
B.C. Giovanella, A.C. Morgan, J.S. Stehlin, L.J. Williams, Selective Lethal Effect of Supranormal Temperatures on Mouse Sarcoma Cells, Cancer Res. 33 (1973), pp. 2568-2578. [cited by applicant]
M.A. Lewis, R.M. Staruch, R. Chopra, Thermometry and ablation monitoring with ultrasound, Int. J. Hyperth. 31 (2015), pp. 163-181. [cited by applicant]
R.M. Arthur, W.L. Straube, J.W. Trobaugh, E.G. Moros, Non-invasive estimation of hyperthermia temperatures with ultrasound, Int. J. Hyperth. 21 (2005), pp. 589-600. [cited by applicant]
R.M. Arthur, W.L. Straube, J. Trobaugh, E.G. Moros, In vivo change in ultrasonic backscattered energy with temperature in motion-compensated images, Int. J. Hyperth. 24 (2008), pp. 389-398. [cited by applicant]
R.M. Arthur, D. Basu, Y. Guo, J.W. Trobaugh, E.G. Moros, 3-D in vitro estimation of temperature using the change in backscattered ultrasonic energy, IEEE Trans. Ultrason. Ferroelectr. Freq. Control. 57 (2010), pp. 1724-… [cited by applicant]
C. Simon, P. VanBaren, E. Ebbini, Two-dimensional temperature estimation using diagnostic ultrasound, IEEE Trans. Ultrason. Ferroelectr. Freq. Control. 45 (1998), pp. 1088-1099. [cited by applicant]
D. Liu, E.S. Ebbini, Real-time 2-D temperature imaging using ultrasound, IEEE Trans. Biomed. Eng. 57 (2010), pp. 12-16. [cited by applicant]
E.S. Ebbini, C. Simon, D. Liu, Real-time ultrasound thermography and thermometry [Life Sciences], IEEE Signal Process. Mag. 35 (2018), pp. 166-174. [cited by applicant]
K.W.A. Van Dongen, M.D. Verweij, A feasibility study for non-invasive thermometry using non-linear ultrasound, Int. J. Hyperth. 27 (2011), pp. 612-624. [cited by applicant]
B. Maraghechi, M.H. Hasani, M.C. Kolios, J. Tavakkoli, Temperature dependence of acoustic harmonics generated by nonlinear ultrasound wave propagation in water at various frequencies, J. Acoust. Soc. Am. 139 (2016), pp.… [cited by applicant]
B. Maraghechi, M.C. Kolios, J. Tavakkoli, Temperature dependence of acoustic harmonics generated by nonlinear ultrasound beam propagation in ex vivo tissue and tissue-mimicking phantoms, Int. J. Hyperth. 31 (2015), pp. … [cited by applicant]
M. Bayat, J.R. Ballard, E.S. Ebbini, In vivo ultrasound thermography in presence of temperature heterogeneity and natural motions, IEEE Trans. Biomed. Eng. 62 (2015), pp. 450-457. [cited by applicant]
B. Maraghechi, Feasibility of noninvasive thermometry in hyperthermia regime using harmonics generated by nonlinear ultrasound wave propagation, Ryerson University, 2016, pp. 1-130. [cited by applicant]
F. Butt, High performance computing for linear acoustic wave simulation, Ryerson University, 2011, pp. 1-127. [cited by applicant]
F. Butt, A. Abhari, J. Tavakkoli, An application of high performance computing to improve linear acoustic simulation, in: Spring Simul. Multi-Conference, Boston, Massachusetts, 2011: pp. 71-78. [cited by applicant]
Mossman “Quantum dots track who gets into cell nucleus” Physorg.com, Sep. 2, 2010, available at http://www.physorg.com/news202628740.html. [cited by applicant]
Wang et al. Nucleic Acid Conjugated Nanomaterials for Enhanced Molecular Recognition. ACS Nano 3 (2009) 2451-2460. [cited by applicant]
You et al. “Incorporation of quantum dots on virus in polycationic solution” Int. J. Nanomedicine, vol. 1, No. 1 (2006), pp. 59-64. [cited by applicant]
Anscombe “Quantum Dots: Small Structures Poised to Break Big” Photonics Spectra, Jul. 2005, pp. 94-96. [cited by applicant]
Mali et al. “Intravitreous Injection of a Membrane Depolarization Agent Causes Retinal Degeneration via Matrix Metalloproteinase-9” Investigative Ophthalmology and Visual Science, vol. 46, No. 6 (2005), pp. 2125-2132. [cited by applicant]
Greenbaum et al. “Application of Photosynthesis to Artificial Sight” paper presented at the Nanoscale Science and Technology in Medicine Symposium, 23rd International Conference of the IEEE Engineering in Medicine and B… [cited by applicant]
Aylott “Optical nanosensors—an enabling technology for intracellular measurements” Analyst, vol. 128 (2003), pp. 309-312. [cited by applicant]
Buck et al. “Optochemical nanosensor PEBBLEs: photonic explorers for bioanalysis with biologically localized embedding” Current Opinion in Chemical Biology, vol. 8 (2004), pp. 540-546. [cited by applicant]
Fehr et al. “Development and use of fluorescent nanosensors for metabolite imaging in living cells” Biochemical Society Transactions, vol. 23, part 1 (2005), pp. 287-290. [cited by applicant]
Ferreira et al. “Downstream processing of plasmid DNA for gene therapy and DNA vaccine applications,” Tibtech, vol. 18 (2000), pp. 380-387. [cited by applicant]
Fei et al. “Glucose nanosensors based on redox polymer/glucose oxidase modified carbon fiber nanoelectrodes” Talanta, vol. 65 (2005), pp. 918-924. [cited by applicant]
Haes et al. “A unified view of propagating and localized surface plasmon resonance biosensors” Anal. Bioanal. Chem, vol. 379 (2004), pp. 920-930. [cited by applicant]
Cullum et al. “The development of optical nanosensors for biological measurements” Tibtech, vol. 18 (2000), pp. 388-393. [cited by applicant]
Hauser and Zhang, “Peptides as biological semiconductors,” Nature, vol. 468 (2010), p. 516. [cited by applicant]
Audero et al. Sporadic Autonomic Dysregulation and Death Associated with Excessive Serotonin Autoinhibition. Science, vol. 321 (2008), pp. 130-133. [cited by applicant]
De Crespigny et al. Magnetic Resonance Imaging Assessment of Cerebral Hemodynamics During Spreading Depression in Rats. Journal of Cerebral Blood Flow and Metabolism, vol. 18 (1998), pp. 1008-1017. [cited by applicant]
Hohne et al. Acetazolamide prevents hypoxic pulmonary vasoconstriction in conscious dogs. J. Appl. Physiol. vol. 97 (2004), pp. 515-521. [cited by applicant]
Rio-Portilla et al. REM Sleep Post-Eye Movement Activation. International Journal of Bioelectromagnetism, vol. 10, No. 4 (2008), pp. 192-208. [cited by applicant]
IBM Press Release, Made in IBM Labs: IBM Scientists Demonstrate World's Fastest Graphene Transistor, Feb. 5, 2010, 1 page. [cited by applicant]
Kurzwiel AI, Engineers envision 2-dimensional graphene metamaterials and 1-atom-thick optical devices. Jun. 10, 2011, 1 page; internet address: http://www.kurzweilai.net/engineers-envision-2-dimensional-graphene-metamat… [cited by applicant]
Erogbogbo et al. Plasmonic gold and luminescent silicon nanoplatforms for multimode imaging of cancer cells. Integr. Biol. 5 (2013) 144-150. [cited by applicant]
Yezhelyev et al., Proton-Sponge-Coated Quantum Dots for siRNA Delivery and Intracellular Imaging. JAm. Chem. Soc. 130 (2008) 9006-9012. [cited by applicant]
Rajan and Raj. Potential Drug Delivery Applications of Chitosan Based Nanomaterials. I.Re.CH.E. 5 (2013) 145-155. [cited by applicant]
Song et al., Tumor Cell Targeting Using Folate-Conjugated Fluorescent Quantum Dots and Receptor-Mediated Endocytosis. Clinical Chemistry 55 (2009) 955-963. [cited by applicant]
Liu et al. Bioconjugated Pluronic Triblock-Copolymer Micelle-Encapsulated Quantum Dots for Targeted Imaging of Cancer: In Vitro and In Vivo Studies. Theranostics 2 (2012) 705-713. [cited by applicant]
Jin et al. Preparation and Characterization of Highly Fluorescent, Glutathione-coated Infrared Quantum Dots for in Vivo Fluorescence Imaging. Int. J. Mol. Sci. 9 (2008) 20440-2061. [cited by applicant]
Liu et al., Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence, PLOS One 8 (2013) e67100, 12 pages. [cited by applicant]
Liu et al., Intracellular Delivery of Nanoparticles and DNAs by IR9 Cell-penetrating Peptides, PLOS One 8 (2013) e64205 (13 pages). [cited by applicant]
Liu et al., Cell-Penetrating Peptide-Functionalized Quantum Dots for Intracellular Delivery. J. Nanosci. Nanotechnol. 10 (2010) 7897-7905. [cited by applicant]
Liu et al., Cellular Internalization of Quantum Dots Noncovalentiy Conjugated with Arginine-Rich Cell-Penetrating Peptides. J. Nanosci. Nanotechnol. 10 (2010) 6534-6543. [cited by applicant]
Xu et al., Nona-Arginine Facilitates Delivery of Quantum Dots into Cells via Multiple Pathways. J. Biomedicine and Biotechnology 2010, Article ID 948543, 11 pages. [cited by applicant]
Delehanty et al., Self-Assembled Quantum Dot-Peptide Bioconjugates for Selective Intracellular Delivery. Bioconjug Chem 17 (2006) 920-927. [cited by applicant]
Narayanan et al., Mimicking cellular transport mechanism in stem cells through endosomal escape of new peptide-coated quantum dots. Scientific Reports 3, Jul. 15, 2013, article No. 2184, 6 pages. [cited by applicant]
Ho et al., Combining QD-FRET and Microfluidics to Monitor DNA Nanocomplex Self-Assembly in Real-Time. J. Vis Exp. 30 (2009) 1432, 3 pages. [cited by applicant]
Biju et al., Delivering quantum dots to cells: bioconjugated quantum dots for targeted and nonspecific extracellular and intracellular imaging. Chem. Soc. Rev. 39 (2010) 3031-3056. [cited by applicant]
Algar and Krull. Toward a Multiplexed Solid-Phase Nucleic Acid Hybridization Assay Using Quantum Dots as Donors in Fluorescence Resonance Energy Transfer. Anal Chem. 81 (2009) 4113-4120. [cited by applicant]
Gao et al. In vivo cancer targeting and imaging with semiconductor quantum dots. Nature Biotechnology 22 (2004) 969-976. [cited by applicant]
Gussin et al. Binding of Muscimol-Conjugated Quantum Dots to GabaC Receptors. J. Am Chem. Soc. 128 (2006) 15701-15713. [cited by applicant]
He et al. Highly Luminescent Water-Dispersible Silicon Nanowires for Long Term Immunofluorescent Cellular Imaging. Angew. Chern. Int. Ed. 50 (2011) 3080-3083. [cited by applicant]
Heiss et al. Image-guided convection-enhanced delivery of muscimol to the primate brain. J Neurosurg. 112 (2010) 790-795. [cited by applicant]
Lugo et al. Remote switching of cellular activity and cell signaling using light in conjunction with quantum dots. Biomedical Optics Express 3. (2012) 447-454. [cited by applicant]
Pappas et al. Nanoscale Engineering of a Cellular Interface with Semiconductor Nanoparticle Films for Photoelectric Stimulation of Neurons. Nano Letters 7 (2007) 513-519. [cited by applicant]
Rosenthal et al. Biocompatible Quantum Dots for Biological Applications. Chem Biol. 18 (2011) 10-24. [cited by applicant]
Templeton. Tiny Q-dots may enable more precise brain surgery. Pittsburgh Post-Gazette, Apr. 10, 2007, 4 pages. [cited by applicant]
Van Rooy et al. Comparison of five different targeting ligands to enhance accumulation of liposomes into the brain. Journal of Controlled Release 150 (2011) 30-36. [cited by applicant]
Wen et al. Theranostic liposomes loaded with quantum dots and apomorphine for brain targeting and bioimaging. International Journal of Nanomedicine 7 (2012) 1599-1611. [cited by applicant]
Zhong et al. Modular design of an ultrahigh-intensity nanoparticle probe for cancer cell imaging and rapid visual detection of nucleic acids. Chem Commun., 48 (2012) 6277-6279. [cited by applicant]
Baker and Baker. Luminescent Carbon Nanodots: Emergent Nanolights. Angew. Chem. Int. Ed. 49 (2010) 6726-6744. [cited by applicant]
Hofmann-Amtenbrink et al. Superparamagnetic nanoparticles for biomedical applications, Nanostructured Materials for Biomedical Applications, (ed. M.C. Tan.) 2009, chap. 5, 119-149. [cited by applicant]
Joeres et al. Quantitative Comparison of Optical Coherence Tomography after Pegaptanib or Bevacizumab in Neovascular Age-Related Macular Degeneration, Ophthalmology 115 (2008) 347-354. [cited by applicant]
Andor Technology, “Transport Across the Nuclear Membrane Using Quantum Dots,” Aug. 23, 2011, available at http://www.andor.com/company/news/?docID=1224. [cited by applicant]
Boyden, “Optogenetics: Using Light to Control the Brain,” The Dana Foundation, Nov. 30, 2011, available at http://www.dana.org/news/cerebrum/detail.aspx?id=34614. [cited by applicant]
Buchen, “Illuminating the Brain,” Nature, vol. 465, May 6, 2010, pp. 26-28. [cited by applicant]
Dixit et al., “Quantum Dot Encapsulation in Viral Capsids,” Nano Letters, vol. 6, No. 9 (2006); pp. 1993-1999. [cited by applicant]
Deisseroth, “Optogenetics,” Nature Methods, Published online Dec. 20, 2010, available at http://www.stanford.edu/group/dlab/papers/deisserothnature2010.pdf. [cited by applicant]
Deisseroth, “Optogenetics: Controlling the Brain with Light [Extended Version],” Scientific American, Published online Oct. 20, 2010, available at http://www.scientificamerican.com/article.cfm?id=optogenetics-controllin… [cited by applicant]
Dubertret et al., “In vivo Imaging of Quantum Dots Encapsulated in Phospholipid Micelles,” Science, vol. 298, No. 5599 (2002), pp. 1759-1762. [cited by applicant]
Gill et al., “Fluorescence Resonance Energy Transfer in CdSe/ZnS-DNA Conjugates: Probing Hybridization and DNA Cleavage,” J. Phys. Chem. B., vol. 109 (2005), pp. 23175-23179. [cited by applicant]
Joo et al., “Enhanced Real-Time Monitoring of Adeno-Associated Virus Trafficking by Virus-Quantum Dot Conjugates,” ACSNano, vol. 5, issue 5 (2011); pp. 3523-3535. [cited by applicant]
Michalet et al., “Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics,” Science, 307, No. 5709 (2005), pp. 538-544. [cited by applicant]
Yizhar et al., “Optogenetics in Neural Systems,” Neuron, vol. 71 (2011), 9-34. [cited by applicant]
Zhang et al., “Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures,” Nature Protocols, vol. 5, No. 3 (2010), pp. 439-456. [cited by applicant]
Aguilera et al. “Systemic in vivo distribution of activatable cell penetrating peptides is superior to cell penetrating peptides,” Integr Biol (Camb), vol. 1, No. 5-6 (2009), pp. 371-381. [cited by applicant]
Kelley. “What Clinicians Need to Know About Molecular Markers in Solid Tumors” Aug. 6, 2010, available at http://www.medscape.org/viewarticle/725989. [cited by applicant]
Nguyen et al. “Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival,” Proc. Nat. Acad. Sci., 107 (2010) 4317-4322. [cited by applicant]
Olson et al. “In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer,” Integr Bioi, 1 (2009) pp. 382-393. [cited by applicant]
Olson et al. “Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases,” Proc. Nat. Acad. Sci. 107 (2010) 4311-4316. [cited by applicant]
Hoare et al. “A Magnetically-Triggered Composite Membrane for On-Demand Drug Delivery,” Nano Lett. 9 (2009) 3651-3657. [cited by applicant]
Mornet et al., Magnetic nanoparticle design for medical diagnosis and therapy, J. Mater. Chem., 14 (2004) 2161-2175. [cited by applicant]
Sexton et al. “A Protective Vaccine Delivery System for In Vivo T Cell Stimulation Using Nanoengineered Polymer Hydrogel Capsules,” ACS Nano, vol. 3, No. 11 (2009), pp. 3391-3400. [cited by applicant]
Alavarez-Lorenzo et al., “Temperature-sensitive chitosan-poly(N-isopropylacrylamide) interpenetrated networks with enhanced loading capacity and controlled release properties” J. Controlled Release 102(3), (2005) 629-64… [cited by applicant]
Balasubramaniam et al., “Poly(N-isopropylacrylamide)-Coated Superaramagnetic Iron Oxide Nanoparticles: Relaxometric and Fluorescence Behavior Correlate to Temperature-Dependent Aggregation” Chem. Mater., 2011, 23, 3348-… [cited by applicant]
Benyettou et al., “Magnetoliposome for alendronate delivery” J. Mater. Chem., 21 (2011) 4813-4820. [cited by applicant]
Budgin et al. “Functionalization of Magnetic Nanoparticles with Amphiphilic Block Copolymers: Self-Assembled Thermoresponsive Submicrometer Particles” Langmuir 28 (2012) 4142-4151. [cited by applicant]
Farokhzad et al., “Impact of Nanotechnology on Drug Delivery” ACS Nano 3(1) 2009, 16-20. [cited by applicant]
Filipa et al., “Polyelectrolyte-Coated Unilamellar Nanometer-Sized Magnetic Liposomes” Langmuir 2009, 25(12), 6793-6799. [cited by applicant]
Pothayee et al., “Magnetic Block Ionomer Complexes for Potential Dual Imaging and Therapeutic Agents” Chem. Mater. 2012, 24, 2056-2063. [cited by applicant]
Tai et al. “Thermosensitive liposomes entrapping iron oxide nanoparticles for controllable drug release” Nanotechnology 20 (2009) 135101 (9 pages). [cited by applicant]
Xu et al. “Controlled Release and Assembly of Drug Nanoparticles via pH-Responsive Polymeric Micelles: A Theoretical Study” J. Phys. Chem. B, 2012, 116 (20), 6003-6009. [cited by applicant]
Booth et al. Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane. The Journal of Cell Biology, vol. 172, No. 6, Mar. 13, 2006, 923-935. [cited by applicant]
Heath et al., Varying Polymer Architecture to Deliver Drugs AAPS J. 9 (2007) Nanotechnology and Drug Delivery, article 26 (http://www.aapsi.org) E235-E240. [cited by applicant]
Jamagin et al. Treatment of cholangiocarcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy. Cancer Gene Therapy 13 (2006) 326-334. [cited by applicant]
Ding et al., Farnesyltransferase inhibitor tipifarnib inhibits Rheb prenylation and stabilizes Bax in acute myelogenous leukemia cells. Haematologica 99 (2014) 60-69. [cited by applicant]
Kleiner et al. Farnesyl and geranylgeranyl transferase inhibitors: an anti-inflammatory effect. Comment to “Inhibition of protein geranylgeranylation and farnesylation protects against graft-versus-host disease via effe… [cited by applicant]
Karp et al. Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia. Blood 119 (2012) 55-63. [cited by applicant]
Hong et al. Phase I Trial of a Combination of the Multikinase Inhibitor Sorafenib and the Farnesyltransferase Inhibitor Tipifarnib in Advanced Malignancies. Clin Cancer Res 15 (2009), 7061-7068. [cited by applicant]
Kurzrock et al. Phase I Study of Alternate-Week Administration of Tipifarnib in Patients with Myelodysplastic Syndrome. Clin Cancer Res 14 (2008) 509-514. [cited by applicant]
Haferlach. Molecular Genetic Pathways as Therapeutic Targets in Acute Myeloid Leukemia. (2008) 400-411. [cited by applicant]
Armand et al. The Emerging Role of Targeted Therapy for Hematologic Malignancies: Update on Bortezomib and Tipifarnib. The Oncologist 12 (2007) 281-290. [cited by applicant]
Yanamandra et al. Tipifarnib and Bortezomib Are Synergistic and Overcome Cell Adhesion-Mediated Drug Resistance in Multiple Myeloma and Acute Myeloid Leukemia. Clin Cancer Res 12 (2006) 591-599. [cited by applicant]
Beaupre et al. R115777 induces Ras-independent apoptosis of myeloma cells via multiple intrinsic pathways. Mol Cancer Ther 3 (2004) 179-186. [cited by applicant]
Leite et al. PE and PS Lipids Synergistically Enhance Membrane Poration by a Peptide with Anticancer Properties. Biophysical Journal 109 (2015) 936-947. [cited by applicant]
Bakalova et al., “Quantum Dot-Conjugated Hybridization Probes for Preliminary Screening of siRNA Sequences” J. Am. Chem. Soc., (2005), 127 (32), pp. 11328-11335. [cited by applicant]
Derfus et al. “Targeted Quantum Dot Conjugates for siRNA Delivery” Bioconjugate Chem., vol. 18, No. 5 (2007) pp. 1391-1396. [cited by applicant]
Ebenstein et al. “Combining atomic force and fluorescence microscopy for analysis of quantum-dot labeled protein-DNA complexes” J. Molecular Recognition, vol. 22, issue 5 (2009), pp. 397-402. [cited by applicant]
Gill et al. “Fluorescence Resonance Energy Transfer in CdSe/ZnS-DNA Conjugates: Probing Hybridization and DNA Cleavage” J. Phys. Chem. B, vol. 109, (2005), pp. 23715-23719. [cited by applicant]
Joo et al. “Enhanced Real-Time Monitoring of Adeno-Associated Virus Trafficking by Virus-Quantum Dot Conjugates” ACS Nano, vol. 5, No. 5 (2011), pp. 3523-3535. [cited by applicant]
Lim et al. “Specific Nucleic Acid Detection Using Photophysical Properties of Quantum Dot Probes” Anal. Chem., vol. 82, No. 3 (2010), 886-891. [cited by applicant]