Systemic and Local Silk-Based Drug Delivery Systems for Cancer Therapy

Abstract

For years, surgery, radiotherapy, and chemotherapy have been the gold standards to treat cancer, although continuing research has sought a more effective approach. While advances can be seen in the development of anticancer drugs, the tools that can improve their delivery remain a challenge. As anticancer drugs can affect the entire body, the control of their distribution is desirable to prevent systemic toxicity. The application of a suitable drug delivery platform may resolve this problem. Among other materials, silks offer many advantageous properties, including biodegradability, biocompatibility, and the possibility of obtaining a variety of morphological structures. These characteristics allow the exploration of silk for biomedical applications and as a platform for drug delivery. We have reviewed silk structures that can be used for local and systemic drug delivery for use in cancer therapy. After a short description of the most studied silks, we discuss the advantages of using silk for drug delivery. The tables summarize the descriptions of silk structures for the local and systemic transport of anticancer drugs. The most popular techniques for silk particle preparation are presented. Further prospects for using silk as a drug carrier are considered. The application of various silk biomaterials can improve cancer treatment by the controllable delivery of chemotherapeutics, immunotherapeutics, photosensitizers, hormones, nucleotherapeutics, targeted therapeutics (e.g., kinase inhibitors), and inorganic nanoparticles, among others.

Research progress of natural silk fibroin and the application for drug delivery in chemotherapies

“…In addition, we also summarize and describe other standard preparation methods, and their advantages and disadvantages are also shown in Table 3 . In these methods, we also find that the size of silk fibroin nanoparticles ranges from 20 nm to 20 μm ( Florczak et al, 2021 ).…”

“…When exogenous substances enter the body, they generally cause immunogenic reactions. However, after degumming, silk fibroin does not contain sericin, so it will not produce immunogenicity ( Florczak et al, 2021 ). Some studies have found that pure sericin can be used as a material with good biocompatibility, so the coexistence of silk fibroin and sericin may lead to an immune response ( Chirila et al, 2013 ).…”

Silk fibroin hydrogels for biomedical applications

“…In the aspect of drug delivery, silk fibroin hydrogels are widely employed as drug delivery carriers due to their selfassembly, processing flexibility, biocompatibility, biodegradability, as well as abilities to capture, retain, protect, and deliver therapeutic payloads. 19,[128][129][130][131] Zhang et al presented an in situ formed silk fibroin hydrogel as a carrier to encapsulate bifactors. In vitro experiments presented that both of the loaded two factors showed no obviously explosive release, while in vivo tests proved an additive effect of VEGF165 and BMP-2 released from the silk hydrogel on promoting angiogenesis and bone regeneration (Figure 8A).…”

“…In the aspect of drug delivery, silk fibroin hydrogels are widely employed as drug delivery carriers due to their self‐assembly, processing flexibility, biocompatibility, biodegradability, as well as abilities to capture, retain, protect, and deliver therapeutic payloads 19,128–131 . Zhang et al.…”

Strategies to functionalize extracellular vesicles against HER2 for anticancer activity

“…Different monoclonal antibodies or fusion moieties have been developed to target the extracellular domain of HER2 [22] , leading to cytostatic effects or cell death when in conjugation with cytotoxic compounds [23,24,25] . These moieties were explored for their targeted delivery potential within different bioformulations, including unilamellar liposomes loaded with chemotherapy agents [26] , gold nanoparticles [27] , or silk nanospheres [28] .…”