Hyaluronic acid wreathed, trio-stimuli receptive and on-demand triggerable nanoconstruct for anchored combinatorial cancer therapy

• Published in: Carbohydrate polymers 2020-12, Vol.249, p.116815, Article 116815
• Main Authors: Poudel, Kishwor, Banstola, Asmita, Tran, Tuan Hiep, Thapa, Raj Kumar, Gautam, Milan, Ou, Wenquan, Pham, Le Minh, Maharjan, Srijan, Jeong, Jee-Heon, Ku, Sae Kwang, Choi, Han-Gon, Yong, Chul Soon, Kim, Jong Oh
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Apoptosis; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; CD44 receptors; Cell Proliferation; Combination therapy; Combined Modality Therapy; Copper - chemistry; Doxorubicin - chemistry; Doxorubicin - pharmacology; Female; Graphite - chemistry; Humans; Hyaluronic acid; Hyaluronic Acid - administration & dosage; Hyaluronic Acid - chemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanosystem; Photochemotherapy; Photothermal agents; Responsiveness; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2020.116815

[Display omitted] •Hyaluronic acid assists in anti-leaking, cleavable, and tumor targeting attributes.•Duo-photo-agents and anticancer drug are nanoengineered for laser responsive therapy.•Escalated release of drug was responded to laser, tumor-localized enzyme, and pH.•Higher tumor accumulation was achieved without off-target retention in normal organs.•Sharp tumor inhibition was observed with significant alteration of tumor markers. Hyaluronic acid (HA) assisted effective internalization into CD44 receptor-overexpressing cancer cells, which could offer an excellent cytotoxic profile and tumor alterations. In this study, duo-photothermal agents (copper sulfide (CuS) and graphene oxide (GO)), chemotherapeutic drug (doxorubicin (DOX)), and targeting moiety (HA) were incorporated into a complexed nanoconstruct for trio-responsive chemo-phototherapy. The nanosystem (CuS(DOX)-GO-HA) was demonstrating its responsive drug release and escalated photothermal behavior. The hyperthermia and photodynamic effect were observed along with efficient ROS generation in the presence of dual photosensitizers. The in vivo biodistribution and photothermal profile reflected a high accumulation and retention of the nanoconstruct in the tumor. Importantly, nanoconstructs effectively inhibit tumor growth based on tumor volume analysis and the altered expression of apoptosis, cell proliferation, and angiogenesis markers. Collectively, these findings suggest that this nanoconstruct has excellent antitumor effects in CD44 overexpressed cells showing the potential for clinical translation in the future.