Photodynamic therapy (PDT) is ineffective against deeply seated metastatic tumors due to poor penetration of the excitation light. Herein, we developed a biomimetic nanoreactor (bio-NR) to achieve synergistic chemiexcited photodynamic-starvation therapy against tumor metastasis. Photosensitizers on the hollow mesoporous silica nanoparticles (HMSNs) are excited by chemical energy in situ of the deep metastatic tumor to generate singlet oxygen (1O2) for PDT, and glucose oxidase (GOx) catalyzes glucose into hydrogen peroxide (H2O2). Remarkably, this process not only blocks the nutrient supply for starvation therapy but also provides H2O2 to synergistically enhance PDT. Cancer cell membrane coating endows the nanoparticle with biological properties of homologous adhesion and immune escape. Thus, bio-NRs can effectively convert the glucose into 1O2 in metastatic tumors. The excellent therapeutic effects of bio-NRs in vitro and in vivo indicate their great potential for cancer metastasis therapy.

Photodynamic therapy (PDT) is a well-established modality for cancer therapy, which locally kills cancer cells when light irradiates a photosensitizer. However, conventional PDT is often limited by the extremely short lifespan and severely limited diffusion distance of reactive oxygen species (ROS) generated by photosensitizer, as well as the penetration depth of visible light activation. Here, we develop a near-infrared (NIR) triggered nanophotosensitizer based on mitochondria targeted titanium dioxide-coated upconversion nanoparticles for PDT against cancer. When irradiated by NIR laser, the nanophotosensitizer could produce ROS in mitochondria, which induced the domino effect on ROS burst. The overproduced ROS accumulated in mitochondria, resulting in mitochondrial collapse and irreversible cell apoptosis. Confocal fluorescence imaging indicated that the mitochondrial targeting and real-time imaging of ROS burst could be achieved in living cells. The complete removal of tumor in vivo confirmed the excellent therapeutic effect of the nanophotosensitizer.

Clinical cancer treatments nowadays still face the challenge of recurrence due to the residual cancer cells and minute lesions in surgeries or chemotherapies. To effectively address the problem, we introduce a strategy for constructing cancer cell nuclear-targeted copper sulfide nanoparticles (NPs) with a significant photothermal effect to completely kill residual cancer cells and prevent local cancer recurrence. The NPs could directly target the tumor cells and further enter the nucleus by the surface modification of RGD and TAT peptides. Under the irradiation of 980 nm near-infrared laser, the NPs rapidly increase the temperature of the nucleus, destroy the genetic substances, and ultimately lead to an exhaustive apoptosis of the cancer cells. In vivo experiments show that the designed NPs could effectively treat cancer and prevent the return of cancer with a single laser irradiation for 5 min. The photothermal therapy strategy with nuclear targeting for cancer therapy and anti-recurrence will provide more possibilities to develop efficient platforms for treating cancer.

A nuclear targeted dual-photosensitizer was developed for photodynamic therapy against multidrug resistant cancer. Multiple reactive oxygen species (ROS) could be generated in the nucleus to directly break DNA double strands with a single 980 nm NIR laser irradiation, regardless of drug resistance.

A size-controllable and facile synthetic strategy has been developed to fabricate a series of hollow mesoporous silica nanoparticles (HMSNs) with tunable hollow cores or shell thicknesses by employing gold nanoparticles (Au NPs) and cetyltrimethylammonium bromide (CTAB) as dual templates. Various sizes of Au NPs and different amounts of tetraethyl orthosilicate contributed to structure-tailored mesoporous silica-coated Au NPs. After calcination, CTAB molecules were completely removed, and Au NPs could still support the silica shell due to the high melting point. HMSNs were ultimately obtained by etching Au NPs. Applications of HMSNs as nanocarriers for delivering drugs were investigated. Significantly, it was flexible and convenient to control drug-loading/releasing behavior of HMSNs just by tuning the hollow cores or shell thicknesses. Intracellular experiments have proven that HMSNs are suitable for delivering drugs. We anticipate that this study could provide an important avenue for the synthesis of HMSNs and further contribute to advancing practical applications of HMSNs in drug delivery systems.