A NIR-driven green affording-oxygen microrobot for targeted photodynamic therapy of tumors.

Photodynamic therapy (PDT) is a light-activated local treatment modality that has promising potential in cancer therapy. However, ineffective delivery of photosensitizers and hypoxia in the tumor microenvironment severely restrict the therapeutic efficacy of PDT. Herein, phototactic Chlorella (C) is utilized to carry photosensitizer-encapsulated nanoparticles to develop a near-infrared (NIR) driven green affording-oxygen microrobot system (CurNPs-C) for enhanced PDT. Photosensitizer (curcumin, Cur) loaded nanoparticles are first synthesized and then covalently attached to C through amide bonds. An in vitro study demonstrates that the developed CurNPs-C exhibits continuous oxygen generation and desirable phototaxis under NIR treatment. After intravenous injection, the initial 660 nm laser irradiation successfully induces the active migration of CurNPs-C to tumor sites for higher accumulation. Upon the second 660 nm laser treatment, CurNPs-C produces abundant oxygen, which in turn induces the natural product Cur to generate more reactive oxygen species (ROS) that significantly inhibit the growth of tumors in 4T1 tumor-bearing mice. This contribution showcases the ability of a light-driven green affording-oxygen microrobot to exhibit targeting capacity and O2 generation for enhancing photodynamic therapy.

Magnetically Actuated Biodegradable Nanorobots for Active Immunotherapy.

An efficient and cost-effective therapeutic vaccine is highly desirable for the prevention and treatment of cancer, which helps to strengthen the immune system and activate the T cell immune response. However, initiating such an adaptive immune response efficiently remains challenging, especially the deficient antigen presentation by dendritic cells (DCs) in the immunosuppressive tumor microenvironment. Herein, an efficient and dynamic antigen delivery system based on the magnetically actuated OVA-CaCO3 -SPIO robots (OCS-robots) is rationally designed for active immunotherapy. Taking advantage of the unique dynamic features, the developed OCS-robots achieve controllable motion capability under the rotating magnetic field. Specifically, with the active motion, the acid-responsiveness of OCS-robots is beneficial for the tumor acidity attenuating and lysosome escape as well as the subsequent antigen cross-presentation of DCs. Furthermore, the dynamic OCS-robots boost the crosstalk between the DCs and antigens, which displays prominent tumor immunotherapy effect on melanoma through cytotoxic T lymphocytes (CTLs). Such a strategy of dynamic vaccine delivery system enables the active activation of immune system based on the magnetically actuated OCS-robots, which presents a plausible paradigm for incredibly efficient cancer immunotherapy by designing multifunctional and novel robot platforms in the future.

Apoptotic Tumor DNA Activated Nanomotor Chemotaxis.

Inspired by the tactic organisms in Nature that can self-direct their movement following environmental stimulus gradient, we proposed a DNase functionalized Janus nanoparticle (JNP) nanomotor system for the first time, which can be powered by ultralow nM to µM levels of DNA. The system exhibited interesting chemotactic behavior toward a DNA richer area, which is physiologically related with many diseases including tumors. In the presence of the subtle DNA gradient generated by apoptotic tumor cells, the cargo loaded nanomotors were able to sense the DNA signal released by the cells and demonstrate directional motion toward tumor cells. For our system, the subtle DNA gradient by a small amount (10 µL) of tumor cells is sufficient to induce the chemotaxis behavior of self-navigating and self-targeting ability of our nanomotor system, which promises to shed new light for tumor diagnosis and therapy.

MnO2-Based Nanomotors with Active Fenton-like Mn2+ Delivery for Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) is an emerging strategy for cancer treatment based on Fenton chemistry, which can convert endogenous H2O2 into toxic ·OH. However, the limited endocytosis of passive CDT nanoagents with low penetrating capability resulted in unsatisfactory anticancer efficacy. Herein, we propose the successful fabrication of a self-propelled biodegradable nanomotor system based on hollow MnO2 nanoparticles with catalytic activity for active Fenton-like Mn2+ delivery and enhanced CDT. Compared with the passive counterparts, the significantly improved penetration of nanomotors with enhanced diffusion is demonstrated in both the 2D cell culture system and 3D tumor multicellular spheroids. After the intracellular uptake of nanomotors, toxic Fenton-like Mn2+ is massively produced by consuming overexpressed intracellular glutathione (GSH), which has a strong scavenging effect on ·OH, thereby leading to enhanced cancer CDT. The as-developed MnO2-based nanomotor system with enhanced penetration and endogenous GSH scavenging capability shows much promise as a potential platform for cancer treatment in the near future.

Near infrared light activation of an injectable whole-cell cancer vaccine for cancer immunoprophylaxis and immunotherapy.

Cancer vaccines play a key role in the prevention and treatment of early and recurrent tumors. Although they have been widely studied during the past few decades, designing an efficient and economical cancer vaccine is still challenging. Here, we propose an injectable live cell cancer vaccine (InLCCV) using live tumor cells as immunogenic sources for cancer immunoprophylaxis and immunotherapy. InLCCV is fabricated by loading live mouse breast cancer cells (4T1 cells), gold nanorods (GNRs), and super-low-dose lipopolysaccharide (LPS) into a biocompatible Pluronic F127 in situ hydrogel matrix. After in situ inactivation by the photothermal effect of GNRs upon near-infrared (NIR) laser irradiation, immunogenic cell death (ICD) of 4T1 cells is induced and tumor-associated antigens (TAAs) together with loaded LPS are released subsequently. Therefore, dendritic cells and macrophages are activated accordingly, further stimulating the systemic anti-tumor immune response. After vaccinating with InLCCV, the tumor-free percentage of the mice is 60% and the survival rate during the observation period reaches up to 80%. For lung metastasis, the metastatic foci are 3.9-fold less than those of the control group. The as-developed InLCCV shows much promise as a potential platform for breast cancer immunoprophylaxis and immunotherapy.

Hyperthermia-Triggered On-Demand Biomimetic Nanocarriers for Synergetic Photothermal and Chemotherapy.

Nanoparticle-based drug delivery systems with low side effects and enhanced efficacy hold great potential in the treatment of various malignancies, in particular cancer; however, they are still challenging to attain. Herein, an anticancer drug delivery system based on a cisplatin (CDDP) containing nanogel, functionalized with photothermal gold nanorods (GNRs) which are electrostatically decorated with doxorubicin (DOX) is reported. The nanoparticles are formed via the crosslinking reaction of hyaluronic acid with the ancillary anticarcinogen CDDP in the presence of DOX-decorated GNRs. The nanogel is furthermore cloaked with a cancer cell membrane, and the resulting biomimetic nanocarrier (4T1-HANG-GNR-DC) shows efficient accumulation by homologous tumor targeting and possesses long-time retention in the tumor microenvironment. Upon near-infrared (NIR) laser irradiation, in situ photothermal therapy is conducted which further induces hyperthermia-triggered on-demand drug release from the nanogel reservoir to achieve a synergistic photothermal/chemo-therapy. The as-developed biomimetic nanocarriers, with their dual-drug delivery features, homotypic tumor targeting and synergetic photothermal/chemo-therapy, show much promise as a potential platform for cancer treatment.