In Situ Nanotransformable Hydrogel for Chemo-Photothermal Therapy of Localized Tumors and Targeted Therapy of Highly Metastatic Tumors

• Published in: ACS applied materials & interfaces 2021-12, Vol.13 (47), p.55862-55878
• Main Authors: Baseeruddin Alvi, Syed, P S, Rajalakshmi, Begum, Nazia, Jogdand, Anil Bankati, Veeresh, Bantal, Rengan, Aravind Kumar
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Biocompatible Materials - administration & dosage; Biocompatible Materials - chemistry; Biological and Medical Applications of Materials and Interfaces; Cell Line; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Doxorubicin - pharmacology; Female; Gold - administration & dosage; Gold - chemistry; Hydrogels - administration & dosage; Hydrogels - chemistry; Injections, Subcutaneous; Liposomes - administration & dosage; Liposomes - chemistry; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Melanoma, Experimental - drug therapy; Melanoma, Experimental - pathology; Melanoma, Experimental - secondary; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; Particle Size; Photothermal Therapy; Surface Properties
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c17054

Metastasis is one of the predisposing factors for cancer-related mortalities worldwide. Patients with advanced cancers (stage IV) receive palliative care with minimal possibility of achieving complete remission. Antibody-based therapeutic modalities are capable of targeting tumors that are confined to a particular location but are ineffective in targeting distant secondary tumors. In the current study, we have developed a smart nano-transforming hydrogel (NTG) that transforms in situ to polymeric nanoparticles (PA NPs) of 100–150 nm when injected subcutaneously. These nanoparticles targeted the primary and secondary metastatic tumors for up to ∼5 and ∼3 days, respectively. The in situ-formed PA NPs also demonstrated a pH-responsive drug release resulting in about ∼80% release within 100 h at 5.8 pH. When tested in vivo, substantial inhibition of lung metastases was observed compared to chemotherapy, thus demonstrating the efficiency of nanotransforming hydrogels in targeting and inhibiting primary and secondary metastatic tumors.