External and Internal Stimuli-Responsive Metallic Nanotherapeutics for Enhanced Anticancer Therapy.

Therapeutic, diagnostic, and imaging approaches based on nanotechnology offer distinct advantages in cancer treatment. Various nanotherapeutics have been presented as potential alternatives to traditional anticancer therapies such as chemotherapy, radiotherapy, and surgical intervention. Notably, the advantage of nanotherapeutics is mainly attributable to their accumulation and targeting ability toward cancer cells, multiple drug-carrying abilities, combined therapies, and imaging approaches. To date, numerous nanoparticle formulations have been developed for anticancer therapy and among them, metallic nanotherapeutics reportedly demonstrate promising cancer therapeutic and diagnostic efficiencies owing to their dense surface functionalization ability, uniform size distribution, and shape-dependent optical responses, easy and cost-effective synthesis procedure, and multiple anti-cancer effects. Metallic nanotherapeutics can remodel the tumor microenvironment by changing unfavorable therapeutic conditions into therapeutically accessible ones with the help of different stimuli, including light, heat, ultrasound, an alternative magnetic field, redox, and reactive oxygen species. The combination of metallic nanotherapeutics with both external and internal stimuli can be used to trigger the on-demand release of therapeutic molecules, augmenting the therapeutic efficacies of anticancer therapies such as photothermal therapy, photodynamic therapy, magnetic hyperthermia, sonodynamic therapy, chemodynamic therapy, and immunotherapy. In this review, we have summarized the role of different metallic nanotherapeutics in anti-cancer therapy, as well as their combinational effects with multiple stimuli for enhanced anticancer therapy.

A Lipophilic IR-780 Dye-Encapsulated Zwitterionic Polymer-Lipid Micellar Nanoparticle for Enhanced Photothermal Therapy and NIR-Based Fluorescence Imaging in a Cervical Tumor Mouse Model.

To prolong blood circulation and avoid the triggering of immune responses, nanoparticles in the bloodstream require conjugation with polyethylene glycol (PEG). However, PEGylation hinders the interaction between the nanoparticles and the tumor cells and therefore limits the applications of PEGylated nanoparticles for therapeutic drug delivery. To overcome this limitation, zwitterionic materials can be used to enhance the systemic blood circulation and tumor-specific delivery of hydrophobic agents such as IR-780 iodide dye for photothermal therapy. Herein, we developed micellar nanoparticles using the amphiphilic homopolymer poly(12-(methacryloyloxy)dodecyl phosphorylcholine) (PCB-lipid) synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The PCB-lipid can self-assemble into micelles and encapsulate IR-780 dye (PCB-lipid-IR-780). Our results demonstrated that PCB-lipid-IR-780 nanoparticle (NP) exhibited low cytotoxicity and remarkable photothermal cytotoxicity to cervical cancer cells (TC-1) upon near-infrared (NIR) laser irradiation. The biodistribution of PCB-lipid-IR-780 showed higher accumulation of PCB-lipid-IR-780 than that of free IR-780 in the TC-1 tumor. Furthermore, following NIR laser irradiation of the tumor region, the PCB-lipid-IR-780 accumulated in the tumor facilitated enhanced tumor ablation and subsequent tumor regression in the TC-1 xenograft model. Hence, these zwitterionic polymer-lipid hybrid micellar nanoparticles show great potential for cancer theranostics and might be beneficial for clinical applications.