Tumor targeted porphyrin-based metal-organic framework for photodynamic and checkpoint blockade immunotherapy.

Photodynamic therapy (PDT) has become a promising approach and non-invasive modality for cancer treatment, however the therapeutic effect of PDT is limited in tumor metastasis and local recurrence. Herein, a tumor targeted nanomedicine (designated as PCN@HA) is constructed for enhanced PDT against tumors. By modified with hyaluronic acid (HA), which could target the CD44 receptor that expressed on the cancer cells, the targeting ability of PCN@HA has been enhanced. Under light irradiation, PCN@HA can produce cytotoxic singlet oxygen (1O2) and kill cancer cells, then eliminate tumors. Furthermore, PCN@HA exhibits fluorescence (FL)/ photoacoustic (PA) effects for multimodal imaging-guided cancer treatment. And PCN@HA-mediated PDT also can induce immunogenic cell death (ICD) and stimulate adaptive immune responses by releasing of tumor antigens. By combining with anti-PD-L1 checkpoint blockade therapy, it can not only effectively suppress the growth of primary tumor, but also inhibit the metastatic tumor growth.

A manual controlled theranostic nanoplatform with real-time photoacoustic quantification of drug release for chemophotothermal therapy.

The development of intelligent nanodrug delivery systems that can visually guide the on-demand quantitative control of drug release has received extensive attention. Herein, two chemotherapeutic drugs, gallic acid and 5-fluorouracil, and Fe(III) were selected to prepare nanomedicine GF-Fe via polyphenol-metal self-assembly and infinite coordination of drug-metal. GF-Fe has good biocompatibility, photothermal properties and photoacoustic (PA) signals. When deferoxamine (DFO) was artificially applied and interacted with GF-Fe, GF-Fe began to disassemble, gallic acid and 5-fluorouracil were gradually released, while the PA signal of the nanomedicine decayed synchronously. Based on this, the relationship between the intensity of the PA signal and the drug release amount was established, so as to realize the precise quantitative control of the drug release in real-time under the guidance of PA imaging. Besides, the combined effect of the two therapeutic drugs in combination with photothermal therapy (PTT) can improve the therapeutic effect, resulting in significant superadditiveness. This nanoplatform constructed by facile synthesis provided good clinical translation potential for the implementation of precise multimodal combination therapy strategies for tumors.

Nanoscale metal-organic framework delivers rapamycin to induce tissue immunogenic cell death and potentiates cancer immunotherapy.

Rapamycin has great potential in the antitumor application, but its therapeutic effect is seriously affected by poor water solubility, targeting ability, and low bioavailability. Here, we constructed a novel composite nanomaterial with PCN-224 as a drug carrier and loaded rapamycin, named R@BP@HA. The nanoplate not only improves targeting, but also synergizes rapamycin with PCN-224 to effectively promote tumor cell apoptosis, which subsequently causes immunogenic cell death (ICD), and shows strong therapeutic effect in 4T1 breast cancer model. The treatment effect depends on three main points:(i)Proapoptotic effect of rapamycin on tumor cells;(ii)ROS production by PCN-224-mediated photodynamic therapy;(iii)ICD induced DC maturation, increased immune response and promoted T cell proliferation and differentiation. This nanoplate offers potential antitumor efficacy in combination with chemotherapy, photodynamic therapy, and immunotherapy.

Construction of Artificial Controllable Aggregation Trojan Horse-Like Nanoplatform for Enhanced NIR-II Photothermal Therapy.

Promoting the aggregation of nanoprobes at tumor sites and realizing precise imaging and treatment of tumors is still one of the important problems to be solved in the field of nanomedicine. Poly-2-phenylbenzobisthiazole (PB) is a novel conjugated polymer with good biocompatibility, excellent photothermal properties in the second near-infrared region (NIR-II), but poor water dispersibility. Herein, a novel self-assembly/polymerization two-in-one strategy was proposed to prepare a new family of poly-2-phenyl-benzobisthiazole-based nanoparticles. Because the hydrophobic polymer PB was well "camouflaged" in the hydrophilic polyphenol-metal networks, the prepared "Trojan horse-like" nanoparticle TF-PB exhibited good water dispersibility. Besides, TF-PB can play a role as a contrast agent for photoacoustic and magnetic resonance dual-modality imaging. When deferoxamine was artificially applied and interacted with TF-PB, the polyphenol-metal networks disintegrated and the hydrophobic material PB was exposed and started hydrophobic aggregation. Thus, it can be applied for precise enhanced photothermal therapy (PTT) in the NIR-II. Meanwhile, the aggregation process enabled non-invasive, fast, and accurate real-time monitoring by self-enhancing photoacoustic imaging. This work has realized the artificially controllable aggregation of photothermal materials in the tumor site, solved the limitations of traditional PTT, and also has good application prospects in clinical therapy.