Synthetic polypeptides and uses thereof
Disclosed herein are novel synthetic polypeptides and uses thereof in the preparation of liposomes. According to embodiments of the present disclosure, the synthetic polypeptide comprises a membrane lytic motif, a masking motif, and a linker configured to link the membrane lytic motif and the masking motif. The linker is cleavable by a stimulus, such as, light, protease, or phosphatase. Once being coupled to a liposome, the exposure to the stimulus cleaves the linker that results in the separation of the masking motif from the membrane lytic motif, which in turn exerts membrane lytic activity on the liposome that leads to the collapse of the intact structure of the liposome, and releases the agent encapsulated in the liposome to the target site. Also disclosed herein are methods of diagnosing or treating a disease in a subject by use of the present liposomes.
1. A liposome comprising,
a center core,
a lipid layer encapsulating the center core, and
a synthetic polypeptide coupled to the lipid layer, wherein the synthetic polypeptide consists of a membrane lytic motif, a masking motif, and a linker configured to link the membrane lytic motif and the masking motif, wherein
the membrane lytic motif is a peptide consisting of SEQ ID NO: 3;
the masking motif is a peptide consisting of 12 negative-charged amino acid residues; and
the linker is a photocleavable or protease-cleavable moiety, wherein
the photocleavable moiety is of the structure of formula (I) or formula (II):
and
the protease-cleavable moiety consists of the amino acid sequence of SEQ ID NO: 23 or 24.
2. The liposome of claim 1 , wherein the center core comprises a therapeutic agent or a reporter molecule.
3. The liposome of claim 2 , wherein the therapeutic agent is selected from the group consisting of an anti-tumor agent, an anti-inflammatory agent, an anti-microbial agent, an anti-oxidant agent, a growth factor, a neuron transmitter, and a protein inhibitor.
4. The liposome of claim 3 , wherein the therapeutic agent is the anti-tumor agent or the protein inhibitor.
5. The liposome of claim 2 , wherein the reporter molecule is a contrast agent, or a fluorescent molecule.
6. A method of diagnosing or treating a disease in a subject, comprising administering to the subject an effective amount of the liposome of claim 1 .
7. The method of claim 6 , wherein the subject is a human.