Progress of Research in In Situ Smart Hydrogels for Local Antitumor Therapy: A Review
Abstract
:1. Introduction
2. Characteristic of In Situ Smart Hydrogels for Local Administration
3. Classification of Smart In Situ Hydrogels
3.1. Temperature Responsiveness
Materials | Therapeutic Agents | Cancer Cell (In Vitro) | Tumor Model (In Vivo) | References |
---|---|---|---|---|
Pluronic F127 | Norcantharidin Doxorubicin | HepG2 cells H22 cells | Hepatocellular carcinoma | [40] |
Pluronic F127 | titanium carbide | 4T1 cells | Breast cancer | [45] |
PLEL | Erlotinib (ERT), | A549 cells | Lung cancer | [44] |
PLEL | indocyanine green R848 CPG ODNs | 4T1 cells luciferase labeled 4T1 cells | Breast cancer | [11] |
Poloxamer 407 | BODIPY-containing, infrared dye-labeled polymeric nanoparticles | GBM-8 cells | Glioblastoma | [46] |
Lys-x005f_x005f PCLA | NA | RAW 263.7 cells | NA | [47] |
PEG-PLLeu | REG BMS202 | CT26-Luc cells | Colorectal cancer | [43] |
chitosan and silk sericin | TF-PpIX heterodimers | 4T1 cells MCF-7 cells | Breast cancer | [38] |
Chitosan and HA | Indocyanine green, imiquimod and cyclophosphamide | A375 cells 4T1 cells | Melanoma Breast cancer | [37] |
Methylcellulose | IR820 | L929 cells NIH3T3 cells 4T1 cells | Breast cancer | [48] |
chitosan | BPNSs CuNPs | A549 cells U87MG cells | Lung cancer hepatocellular carcinoma Glioblastoma | [49] |
Pluronic F127 | BPNSs DTX | 4T1 cells | Breast cancer | [41] |
PCLA-PEG-PCLA | curcumin-loaded mPEG-PLA nanopolymersome | C6 tumor cells | Glioma tumor | [42] |
3.2. pH Responsiveness
Materials | Therapeutic Agents | Cancer Cell (In Vitro) | Tumor Model (In Vivo) | Reference |
---|---|---|---|---|
KKFKFEFEF peptide, 2,3-DA | MTX | 4T1 breast cancer cells | Breast cancer | [58] |
4armPEG-benzaldehyde, N-carboxyethyl chitosan | DOX | HepG2 cells | Hepatocellular carcinoma | [56] |
FOE octapeptide | DOX | 4T1 breast cancer cells | Breast cancer | [59] |
octa-x005f peptide FEFEFRFK | Paclitaxel | HepG2 cells | H22 tumor | [60] |
Dextran phosphate | Prospidine | HEp-2 cells HeLa cells | Cervical epithelial carcinoma | [61] |
F-127, Citric acid, 1, 8- Octanediol, PEG-PEI | DOX | A375 cancer cell | Human malignant melanoma | [62] |
metal–organic nanoparticles, zinc nitrate | DOX, glucose oxidase | 4T1 breast cancer cells | Breast cancer | [63] |
PCLA, boronic acid | DOX | HepG2 cells | HepG2 liver cancer | [64] |
Chitosan | 5-Fluorouracil | HaCaT | Melanoma | [65] |
3.3. Light Responsiveness
Materials | Therapeutic Agents | Cancer Cell (In Vitro) | Tumor Model (In Vivo) | Reference |
---|---|---|---|---|
Alginate | PpIX-modified Fe3O4 nanoparticles, aPD-L1 | 4T1 cells | 4T1 breast cancer | [83] |
Ti3C2, agarose, and protein | HGF, TNF-alpha | DU145 cells | HCT116 colon cancer | [84] |
Agarose | WO2.9 nanosheets, nitric oxide (NO) precursor | 4T1 cells, C666-1 cells, MCF-7 cells, J774 cells | Breast cancer, hepatoma carcinoma | [85] |
Silica colloidal crystal, MAA, HEMA, EGDMA, HMPP | DOX | NIH-3T3 cells, T24 cells | T24 bladder cancer | [86] |
Gelatin | BSA/AgNP | B16F10 cells | B16F10 melanoma | [87] |
GelMA | Abraxane® | MDA-MB-231 cells, MCF-7 cells | NA | [79] |
3.4. Magnetic-Field Responsiveness
3.5. Ionic Strength Responsiveness
3.6. Enzyme Responsiveness
3.7. Electricity Responsiveness
3.8. Other Responsiveness
4. Summary and Outlook
- Most localized therapy strategies of in situ hydrogels are mainly limited to superficial tumors and are unavailable for distant lesions or metastases or deep tumors because external stimuli such as light are unable to penetrate deep tissues. The intratumoral injection technique for deep tumors is also a problem for local administration. Optimistically, with the aid of modern imaging techniques such as ultrasound, CT guidance or laparoscopy, safe and precise injections can be achieved in some deep solid tumors.
- Smart hydrogels have been advanced in recent decades with the development of biomaterials. Although the short-term biocompatibility and safety of most new synthesized biomedical materials have been assessed, the long-term toxicity remains inconclusive and requires further investigation and clarification. Therefore, it can be predicted that the safety, especially the long-term safety of biomedical materials, will become an essential research aspect in the future.
- The responsiveness of hydrogels to the stimuli in human tumor tissues might be different from that observed in the laboratory. Even in vitro experiments under pathophysiological conditions sometimes might not be the same as in vivo studies. Moreover, the in vivo reproducibility of the response of smart hydrogels can be influenced by individuals at different cancer stages. Thus, designing personalized and precisely tunable hydrogel systems with dual-stimulus or muti-stimulus responses to meet different patients’ needs is an important and promising direction. Notably, smart hydrogels that are sensitive to biological factors such as enzymes or antibodies have great potential for conduct precise and individual anticancer therapy in combination with other stimuli, which allows precise targeted delivery of the loaded drug.
- The clinical translation of such in situ hydrogel systems still remains difficult. Numerous studies have stopped at the stage of preclinical studies, while a few in situ smart hydrogels have entered clinical trials. This might be ascribed to the complex synthetic routes of some polymers and the complicated preparation process of drug-loaded hydrogels, resulting in difficulty in industrial-scale production. Accordingly, the design of simple and single-step preparations of such hydrogels is another promising direction. Moreover, standardized operation and testing processes are indispensable for realizing industrial production and ensuring their reproducibility.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Zhao, J.; Wang, L.; Zhang, H.; Liao, B.; Li, Y. Progress of Research in In Situ Smart Hydrogels for Local Antitumor Therapy: A Review. Pharmaceutics 2022, 14, 2028. https://doi.org/10.3390/pharmaceutics14102028
Zhao J, Wang L, Zhang H, Liao B, Li Y. Progress of Research in In Situ Smart Hydrogels for Local Antitumor Therapy: A Review. Pharmaceutics. 2022; 14(10):2028. https://doi.org/10.3390/pharmaceutics14102028
Chicago/Turabian StyleZhao, Juan, Ling Wang, Haiwei Zhang, Bin Liao, and Yongsheng Li. 2022. "Progress of Research in In Situ Smart Hydrogels for Local Antitumor Therapy: A Review" Pharmaceutics 14, no. 10: 2028. https://doi.org/10.3390/pharmaceutics14102028
APA StyleZhao, J., Wang, L., Zhang, H., Liao, B., & Li, Y. (2022). Progress of Research in In Situ Smart Hydrogels for Local Antitumor Therapy: A Review. Pharmaceutics, 14(10), 2028. https://doi.org/10.3390/pharmaceutics14102028