pH-Triggered Charge-Reversal Silk Sericin-Based Nanoparticles for Enhanced Cellular Uptake and Doxorubicin Delivery

Silk-based nanoparticles have been exhibiting an increasing potential for use as drug delivery systems due to their great versatility. To extend applications of silk sericin in nanomedicine and improve the performance of silk-based nanoparticles in drug delivery, a facile two-step cross-linking is attempted, for the first time, to fabricate surface charge-reversal silk sericin-based nanoparticles (SSC@NPs) by introducing chitosan into silk sericin. The results suggest stable SSC@NPs are formed with a negative surface charge in a neutral environment. Under mildly acidic conditions, however, surface charge of SSC@NPs undergoes a negative-to-positive conversion. It proves that pH can regulate surface charge of SSC@NPs. It is the increased amino/carboxyl ratio in SSC@NPs that explains the underlying mechanism of the charge conversion property of SSC@NPs. Furthermore, the positively charged SSC@NPs triggered by tumor acidic microenvironment (pH 6.0) result in a 6.0-fold higher cellular uptake than the negatively charged counterparts at pH 7.4. In addition, an anticancer drug doxorubicin (DOX) is readily loaded into SSC@NPs and released in a pH-dependent manner. This work provides a simple method to fabricate smart pH-responsive nanoparticles for anticancer drug delivery

Efficient Tumor Immunotherapy through a Single Injection of Injectable Antigen/Adjuvant-Loaded Macroporous Silk Fibroin Microspheres

Synthetic or natural materials have been used as vaccines in cancer immunotherapy. However, using them as vaccines necessitates multiple injections or surgical implantations. To tackle such daunting challenges, we develop an injectable macroporous Bombyx mori (B. mori) silk fibroin (SF) microsphere loaded with antigens and immune adjuvants to suppress established tumors with only a single injection. SF microspheres can serve as a scaffold by injection and avoid surgical injury as seen in traditional scaffold vaccines. The macroporous structure of the vaccine facilitates the recruitment of immune cells and promotes the activation of dendritic cells (DCs), resulting in a favorable immune microenvironment that further induces strong humoral and cellular immunity. We have also modified the vaccine into a booster version by simply allowing the antigens to be adsorbed onto the SF microspheres. The booster vaccine highly efficiently suppresses tumor growth by improving the cytotoxic T lymphocyte (CTL) response. In general, these results demonstrate that the macroporous SF microspheres can serve as a facile platform for tumor vaccine therapy in the future. Since the SF microspheres are also potential scaffolds for tissue regeneration, their use as a vaccine platform will enable their applications in eradicating tumors while regenerating healthy tissue to heal the tumor-site cavity

Design of Bombyx mori (B. mori) Silk Fibroin Microspheres for Developing Biosafe Sunscreen

Sunscreens play a crucial role in protecting the skin from ultraviolet (UV) damage. However, present commercial sunscreens have a tendency to generate free radicals in the UV window, resulting in serious inflammatory responses and health problems. In this study, we demonstrate that silk fibroin microspheres (SFMPs) assembled from regenerated silk fibroin (SF) could scavenge free radicals while preventing UV irradiation and thus present a promising sunscreen. The SFMP reflected more UV light than SF and presented a higher stability than that of organic commercial sunscreens. In vitro analysis proved that SFMP could more efficiently scavenge the hydroxy radical and reduce the intracellular reactive oxygen than titanium dioxide (TiO2). In vivo experiments exhibited that SFMP provided stronger skin protection against UV irradiation than commercial sunscreens and TiO2. Furthermore, SFMP treatment significantly inhibited the skin inflammatory response. This work suggests that the SFMP has great potential to be developed into a biosafe sunscreen

Additional file 1 of Injectable Bombyx mori (B. mori) silk fibroin/MXene conductive hydrogel for electrically stimulating neural stem cells into neurons for treating brain damage

Additional file 1: Table S1. The content of titanium (Ti) in each group of SF/MXene hydrogels. Figure S1. Young’s modulus of SF-based hydrogels with varying MXene content after injection with a 26-gauge needle. Figure S2. Loss modulus G’’ of SF-based hydrogels with varying MXene content. Figure S3. The swelling of SF-based hydrogels with varying MXene content. Figure S4. Percentage of viable cells in each group. Figure S5. Proportions of neurons (A) and glial cells (B) in each group on days 3 and 10. Figure S6. Quantitative analysis of fluorescence intensity of β-tubulin III-positive cells (A) and GFAP-positive cells (B). Figure S7. Volcano plot depicting expression level variations between the SF/MXene + ES and SF groups. Red dots illustrate significantly upregulated genes, green dots indicate notably downregulated genes and gray dots signify genes with no significant differential expression. Figure S8. Quantification of Evans blue was tested by the spectrophotometry after the brain tissues were lysed. Figure S9. In vivo degradation curve of the implanted SF/MXene hydrogel. Table S2. The sequences of primers used for the qPCR analysis. Video S1. Performance of rats in the TBI group on the balance beam. Video S2. Performance of rats in the SFMC + E group on the balance beam