Cleavable Poly(Ethylene Glycol) Branched Chain-Modified Antheraea Pernyi Silk Fibroin as A Gene Delivery Carrier

Abstract

Aim: To obtain a gene carrier that can effectively deliver loaded therapeutic genes to tumor cells, avoid toxic effects on normal cells and reduce nonspecific adsorption of plasma proteins. Methods: The conjugate of poly(ethylene glycol) (PEG) and MMP2SSP (PEG-MMP2SSP) was covalently coupled to cationized Antheraea pernyi silk fibroin (CASF) through disulfide bond exchange reaction to obtain a PEG-MMP2SSP-modified CASF (CASFMP). Results: The PEG chains were effectively cleaved from the CASFMP by MMP2. CASFMP/pDNA complexes inhibited human fibrosarcoma cell proliferation, and its cytotoxicity to human normal embryonic kidney cells was significantly lower than that of poly(ethylenimine)/pDNA after coculturing with cells for 24 h. Conclusion: CASFMP is a promising compound for use in gene therapy.

Nanoparticle based medicines: approaches for evading and manipulating the mononuclear phagocyte system and potential for clinical translation

“…32 Examples of this technique include a micelle incorporating zwitterionic carbomethyl chitosan to assist with endosomal escape 83 and a micelle which reveals a cationic surface after PEG is cleaved in the tumour microenvironment following enzymatic cleavaged. 84 Alternatively, effective uptake can be achieved whilst keeping a neutral surface charge by incorporating ligands which target internalising extracellular receptors. 85…”

Progress in silk and silk fiber-inspired polymeric nanomaterials for drug delivery

“…Recent studies have found that some of these fibers expand the design space for silk-based materials by having more reactive residues and different mechanical properties. Recently, silk fibroin from Antheraea assamensis (Baruah et al, 2020;Asapur et al, 2022), Antheraea pernyi (Liu et al, 2021), and sericin from Antheraea mylitta (Nayak et al, 2021) have all been used in the development of nanoparticle DDS (Table 1). Asapur et al (2022) characterized the secondary structure of nanoparticles synthesized from Antheraea assamensis fibroin by desolvation and radiolysis methods.…”

“…Baruah et al (2020) evaluated the release of doxorubicin from Antheraea assamensis fibroin particles made by desolvation and found efficient drug loading, and that the DDS increased the effectiveness relative to free doxorubicin of the cytotoxic effect on MDA-MB-231 cancer cells. Liu et al (2021) took advantage of the abundant reactive sites present in silk fibroin from Antheraea pernyi in the creation of their stimuli responsive DDS. They prepared particles from cationized Antheraea pernyi fibroin for gene delivery to cancer cells by desolvation in DMSO.…”

“…This allowed for limiting opsonization without sacrificing transfection when MMP-2 (highly expressed in the tumor microenvironment) cleaves the PEG in vitro. They demonstrated decreased protein adhesion and successful transfection to HEK293 cells (Liu et al, 2021). In addition to leveraging the biodiversity of silk fiber producing species to design novel polymeric nanomaterials for DDS, researchers have also recently been producing recombinant proteins inspired by silk fibers to create targeted DDS.…”