Self-adaptive hydrogel for breast cancer therapy via accurate tumor elimination and on-demand adipose tissue regeneration

The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment. Herein, a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination, on-demand adipose tissue regeneration and effective infection inhibition. The hydrogel consisted of thiol groups ended polyethylene glycol (SH-PEG-SH) and doxorubicin encapsulated mesoporous silica nanocarriers (DOX@MSNs) double crosslinked hyaluronic acid (HA) after loading of antibacterial peptides (AP) and adipose-derived stem cells (ADSCs). A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release, meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs, which contributed to the selective chemotherapy in tumor cells with over-expressed esterase. The bond cleavage between MSNs and HA would also cause the swelling of the hydrogel, which not only provide sufficient space for the growth of ADSCs, but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy, resulting in the on-demand regeneration of adipose tissue. Moreover, the sustained release of AP could be simultaneously triggered along with the size change of hydrogel, which further avoided bacterial infection to promote tissue regeneration. A self-adaptable size and dual responsive hydrogel consisting hyaluronic acid (HA), adipose-derived stem cells (ADSCs), doxorubicin (DOX) loaded mesoporous silica nanocarriers (MSNs) and antibacterial peptides (AP) were fabricated via click chemistry and coordinate chemistry to treat breast cancer. The hydrogel exhibits a highly selective drug delivery for effective tumor therapy, triggers the AP avoiding microbial infections to promote tissue regeneration and completes filling the defects after chemotherapy by pre-seeded adipose stem cells regenerate new adipose tissue. [Display omitted]