Melanin-like nanoparticles loaded with an angiotensin antagonist for an improved photothermal cancer therapy.

An abnormal tumor growth induces solid stress in tumors, thus reducing blood perfusion. As a result, the impaired blood perfusion, with dense interstitial matrix in tumors significantly reduces the penetration and efficacy of nanotherapeutics. In this study, we have developed a losartan-loaded polydopamine nanoparticle (PLST) for the enhanced delivery of nanoparticles to tumors and improved photothermal cancer therapy. Losartan, an angiotensin inhibitor, is also able to alleviate the solid stress in tumors. It was laden on polydopamine nanoparticles via π-π stacking and was released upon tumor extracellular acidity. PLST reduced collagen production in vitro along with the lowered expression of profibrotic factors of TGF-ß1, CCN2, and TIMP-1. The in vivo studies reveal that PLST reduced solid stress in tumors, and the amount of PLST accumulated in tumors was enhanced. The efficiency of the photothermal ablation of tumors was significantly enhanced by using PLST.

Melanin-like nanoparticles decorated with an autophagy-inducing peptide for efficient targeted photothermal therapy.

Photothermal therapy efficiently ablates tumors via hyperthermia but inevitably induces serious side effects including thermal damage to normal tissues, inflammations and enhanced risk of tumor metastasis. In this study, we fabricated a dual peptide decorated melanin-like nanoparticle for tumor-targeted and autophagy-promoted photothermal therapy in pursuit of improved cancer treatment. The multifunctional nanoparticle was composed of dual peptide RGD- and beclin 1-modified and PEGylated melanin-like polydopamine nanoparticles. Beclin 1-derived peptide modified on the nanoparticle up-regulated autophagy in cancer cells and further sensitized the tumors to photothermal ablation. RGD decorated on the particle surface enhanced the selectivity and cellular uptake of polydopamine nanoparticles by breast cancer cells. In vivo therapeutic experiments revealed that the tumor-targeted and autophagy promotion-associated photothermal therapy efficiently regressed tumors at a low temperature around 43 °C. The study provides a novel and efficient strategy to improve the efficiency of photothermal therapy via the up-regulation of autophagy in tumor cells.

A Carboxyl-Terminated Dendrimer Enables Osteolytic Lesion Targeting and Photothermal Ablation of Malignant Bone Tumors.

Malignant bone tumor accompanied by tumor-associated osteolysis remains a challenging task in clinical practice. Nanomedicines engineered with bone-targeting ligands, such as alendronate and pamidronate, are developed for targeted delivery of therapeutic agents to bone tumors. However, these targeting strategies usually show relatively poor selectivity toward the healthy skeletons and the osteolytic lesions because of the high binding affinity of bisphosphonates with all the bone tissues. Here, we reported a carboxyl-terminated dendrimer as the candidate to preferentially deliver therapeutic nanoparticles to the osteolytic lesions in a malignant bone tumor model. The high density of carboxyl groups on dendrimer surface endow the polymer with natural bone-binding capability. The dendrimer encapsulated with platinum nanoparticle predominantly accumulates at the osteolytic lesions around bone tumors rather than at healthy bone tissues in vivo. The therapeutic experiments reveal that the dendrimer-mediated photothermal therapy efficiently suppresses bone tumors and osteolysis, and the anionic polymer exhibits minimal cytotoxicity and hematologic toxicity. The results suggest that the carboxyl-terminated dendrimer is a promising candidate for selective delivery of therapeutics to the osteolytic lesions and photothermal treatment of malignant bone tumors.

One stone with two birds: Phytic acid-capped platinum nanoparticles for targeted combination therapy of bone tumors.

Targeted drug delivery to malignant bone lesions remains a challenging task in the treatment of bone tumors. In this article, we reported a naturally occurring phytic acid (PA) with both bone-targeting capability and anticancer activity. The PA-capped platinum nanoparticles showed high affinity to hydroxyapatite in vitro and in vivo, and maintained both the inherent anticancer ability of PA and photothermal effect of platinum nanoparticles. PA-capped nanoparticles displayed a 4-fold higher accumulation in the osteolytic lesions than sodium citrate-templated ones, and efficiently inhibited bone tumor growth and the tumor associated-osteolysis upon exposure to a near-infrared light. This study provides a novel and efficient strategy to prepare bone-targeted nanoparticles with inherent anticancer activity for combination therapy of malignant bone tumors.

Autophagy inhibition enabled efficient photothermal therapy at a mild temperature.

The heterogeneously-distributed hyperthermia in nanomaterial-mediated photothermal therapy commonly results in incomplete tumor eradication and serious damage of health tissue. Here, we found autophagy was activated in cancer cells underwent photothermal therapy and the inhibition of autophagy significantly enhanced the efficacy of photothermal killing of cancer cells. A formulation of chloroquine-loaded polydopamine nanoparticles was developed for sensitized photothermal cancer therapy, and the in vitro and in vivo study demonstrated that inhibition of autophagy remarkably augmented the efficacy of photothermal therapy, leading to efficient tumor suppression at a mild temperature. The regulation of autophagy provides a new route to increase the efficacy of photothermal cancer therapy.

Osteotropic peptide-mediated bone targeting for photothermal treatment of bone tumors.

The treatment of bone tumors is a challenging problem due to the inefficient delivery of therapeutics to bone and the bone microenvironment-associated tumor resistance to chemo- and radiotherapy. Here, we developed a bone-targeted nanoparticle, aspartate octapeptide-modified dendritic platinum-copper alloy nanoparticle (Asp-DPCN), for photothermal therapy (PTT) of bone tumors. Asp-DPCN showed much higher affinity toward hydroxyapatite and bone fragments than the non-targeted DPCN in vitro. Furthermore, Asp-DPCN accumulated more efficiently around bone tumors in vivo, and resulted in a higher temperature in bone tumors during PTT. Finally, Asp-DPCN-mediated PTT not only efficiently depressed the tumor growth but also significantly reduced the osteoclastic bone destruction. Our study developed a promising therapeutic approach for the treatment of bone tumors.

Dendrimer-Templated Ultrasmall and Multifunctional Photothermal Agents for Efficient Tumor Ablation.

Ultrasmall and multifunctional nanoparticles are highly desirable for photothermal cancer therapy, but the synthesis of these nanoparticles remains a huge challenge. Here, we used a dendrimer as a template to synthesize ultrasmall photothermal agents and further modified them with multifunctional groups. Dendrimer-encapsulated nanoparticles (DENPs) including copper sulfide, platinum, and palladium nanoparticles possessed a sub-5 nm size and exhibited an excellent photothermal effect. DENPs were further modified with TAT or RGD peptides to facilitate their cellular uptake and targeting delivery to tumors. They were also decorated with fluorescent probes for real-time imaging and tracking of the particles' distribution. The in vivo study revealed RGD-modified DENPs efficiently reduced the tumor growth upon near-infrared irradiation. In all, our study provides a facile and flexible scaffold to prepare ultrasmall and multifunctional photothermal agents.