Injectable Hydrogels as Unique Platforms for Local Chemotherapeutics‐Based Combination Antitumor Therapy

Abstract

Different strategies of chemotherapeutics‐based combination cancer therapy have presented enhanced antitumor efficiency and are widely used in clinical cancer treatments. However, several drawbacks of the systems for systemic administration, including low drug accumulation at tumor sites and significant systemic side effects limit their efficacy and application in the clinic. Local drug co‐delivery systems based on injectable hydrogels may have considerable advantages, such as a facile drug‐delivery procedure, targeted delivery of antitumor agents to tumor sites in a sustained manner, and markedly reduced systemic toxicities. Thus, in recent years, these systems have received increasing attention and consequently various injectable hydrogels have been tested as platforms for local chemotherapeutics‐based combination antitumor therapy. In this review, the focus is on recent advances in injectable hydrogel‐based drug co‐delivery systems for local combination antitumor therapy, including multiple chemotherapeutics combination therapy, chemo‐immunotherapy, chemo‐radiotherapy, and hyperthermia‐chemotherapy. Moreover, the rationale and preparation of local co‐delivery systems are summarized and discussed.

Preparation and applications of peptide-based injectable hydrogels

“…Injectable implant hydrogels are a class of uid hydrogels that can be injected into the body directly to easily ll irregular shapes and form freestanding solids in defective parts. 17,18 Compared to systemic injections, injectable hydrogel-based local treatments have great potential biomedical applications due to their signicant drug accumulation at lesion sites, sustained release and markedly reduced systemic side effects. 18 Hydrogels are mainly constructed by physical and chemical cross-linking (Table 1).…”

“…17,18 Compared to systemic injections, injectable hydrogel-based local treatments have great potential biomedical applications due to their signicant drug accumulation at lesion sites, sustained release and markedly reduced systemic side effects. 18 Hydrogels are mainly constructed by physical and chemical cross-linking (Table 1). 19…”

“…Chemically cross-linked hydrogels are covalently crosslinked networks formed by covalent bonds generated by copolymerization or condensation polymerization initiated by traditional synthesis methods, photo-polymerization, 32 enzyme polymerization, 7 radiation polymerization, 33 and other technologies. 6,18 Compared to physically cross-linked hydrogels, chemically cross-linked hydrogels have stable structures, high strength, slow degradation, good reaction controllability, and easy operation, which are benecial to their biomedical applications. However, due to the introduction of reactive cross-linking agents or functional groups with reactivity, the reaction between the active reactive group in the polypeptide chain and the cross-linking agent creates the gel network, which accompanies by chemical reaction in the process of gel formation.…”

Thermosensitive Polypeptide Hydrogels Co‐Loaded with Two Anti‐Tumor Agents to Reduce Multi‐Drug Resistance and Enhance Local Tumor Treatment

“…[ 26,27 ] In particular, locoregional combination therapy by the co‐delivery of more than one therapeutics simultaneously is of increasing interest for both tumor treatment and tissue regeneration, due to its unique advantages including predictable and enhanced drug concentration at pathological sites, sustained drug release profiles, and reduced systemic toxicity. [ 28–36 ] Thermosensitive polymeric hydrogels as an important type of implantable macroscale drug‐delivery platforms, have been widely used to co‐deliver various therapeutic agents for local cancer treatment. [ 28,35 ] Our previous work also demonstrated that thermosensitive hydrogel could leverage the therapeutical outcomes of different drugs and enhance their combination for anti‐cancer efficiency.…”

“…[ 28–36 ] Thermosensitive polymeric hydrogels as an important type of implantable macroscale drug‐delivery platforms, have been widely used to co‐deliver various therapeutic agents for local cancer treatment. [ 28,35 ] Our previous work also demonstrated that thermosensitive hydrogel could leverage the therapeutical outcomes of different drugs and enhance their combination for anti‐cancer efficiency. [ 30,37,38 ] Nevertheless, despite enhanced anti‐tumor efficacy with local sustained co‐delivery of multiple anti‐tumor agents, the combined effects of this strategy on development of MDR have been studied inadequately.…”