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Inventing a tumor-responsive theranostic nanoconstruct shows great potential for improving the therapeutic outcome on cancer. Herein, a facile in situ growth strategy based on polyoxometalate (POM) integrated with the mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO2) has been developed. The product was named as USP, and can be triggered by 808 nm light for cancer theranostic. The POM is ultra-sensitive to the intratumoral acidity and reducibility, which enables the photothermal conversion of 808 nm photon for photothermal therapy (PTT). The POM endows the nanostructure highly hydrophilic surface, which is very significant for in vivo application. Need to point out, the photothermal conversion ability of POM enhances the inner temperature of doxorubicin (DOX)-loaded USP (USP-DOX), realizing a bioresponsiveness and NIR photon co-enhanced chemo-photothermal therapy. The POM can also obviate the DOX leakage in normal tissues while accelerate DOX release in tumor tissues under NIR irradiation. Significantly, the POM endows the nanomedicine self-assemble property in acidic tumor microenvironment, which is highly beneficial for enhancing intratumoral accumulation. Highly effective anticancer therapy of the developed USP-DOX has been validated by the in vitro and in vivo assays. The Gd3+/Nd3+/Yb3+/Er3+ co-doped UCNPs ensure the nanosystem MRI/CT/UCL imaging functions, thus achieving the integration of therapy and diagnosis.

The tumor microenvironment (TME) is complex in composition and unique in nature, and is closely related to the growth, invasion and metastasis of tumor cells. Improving and remodeling the TME to return it to a normalized state can fundamentally disrupt the environment and/or nutrient supply on which tumor cells depend. To achieve this goal, based on the unique physicochemical properties and biological effects of CaO2, we designed and constructed a Ca2+ nanogenerator (named as CaO2-Cu/ICG@PCM) that enables H2O2/O2 self-supplementation and GSH depletion. The 808 nm laser induces the heat generation of photosensitizer indocyanine green (ICG) to initiate a series of reactions, followed by the production of copper ions, H2O2, O2 and large amounts of Ca2+, which can eventually lead to the combined treatment of photodynamic therapy (PDT), chemodynamic therapy (CDT) and calcium overload. Additionally, the reaction process is accompanied by the generation of Ca(OH)2, which greatly improves the acidic environment of TME and effectively promotes the oxidation process of GSH by H2O2, achieving the purpose of remodeling TME. It is worth mentioning that a large amount of free Ca2+ accumulating in tumor cells can rapidly initiate the process of calcium overload and calcification, which can not only play a role in tumor suppression, but also assist CT imaging to detect the effect of treatment. Thus, CaO2-Cu/ICG@PCM could be a promising candidate for bioimaging and tumor therapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) combined treatment guided by imaging diagnosis has brought the cancer treatment into a new stage. But simple nanoplatforms with multifunctional therapeutic performance are rarely designed. Herein, we adopt ball-milling method to fabricate spherical BiAgOS nanoparticles as photosensitizer to apply for 808 nm near-infrared (NIR) light triggered PDT and PTT co-therapy. The polyethylene glycol (PEG) modified BiAgOS NPs show a great absorption in the range of visible light to near-infrared region. Under 808 nm laser irradiation, BiAgOS-PEG NPs have obvious photothermal and photosensitive effects together with excellent X-ray computed tomography (CT) imaging function. The in vitro and in vivo experiments exhibit that the BiAgOS-PEG NPs have good biocompatibility, excellent tumor cells inhibition effects simultaneously. Our finding described the first use of BiAgOS-PEG NPs as a semiconductor photosensitizer for anti-cancer treatment, providing a promising strategy to fabricate this kind of material for imaging guided NIR light induced combined tumor treatment.

Synergistic therapy with different treatment mechanisms is an emerging strategy to improve antitumor efficiency. Here, a diversified nanoplatform (Ag2S@MSN-TGF) is synthesized by coating mesoporous silica on Ag2S nanoparticles (NPs), followed by loading hypoxia-active prodrug (tirapazamine) insides the mesoporous silica and coating glucose oxidase (GOx) on the surface. Considering that the degree of hypoxia in tumors is not high enough, GOx is combined with hypoxia-active tirapazamine prodrug, and two important functions are realized. One is the consumption of oxygen to enhance the hypoxic environment and promote the curative effect of tirapazamine, and the other is the consumption of glucose to achieve starvation treatment. Additionally, we take the lead in using Ag2S NPs for second near-infrared (NIR-II, 1064 nm) excited photothermal therapy (PTT). The photothermal conversion efficiency (44.7%) of Ag2S@MSN-TGF is even better than that under 808 nm laser irradiation (38.2%). Finally, in vivo NIR-II fluorescence imaging well demonstrated that Ag2S@MSN-TGF can offer an obvious tracking effect for the therapeutic process. Therefore, superior to any single therapeutic mode, our designed Ag2S@MSN-TGF demonstrates an excellent tumor inhibition effect in vitro and in vivo due to synergistic starvation, hypoxia-active prodrug treatment and PTT effect, suggesting the significant prospect of NIR-II imaging guided antitumor therapy.

The strategy of combining imaging and treatment has been shown as a widely studied and promising approach. In this work, we first integrated copper sulfide (CuS) nanoparticles and black phosphorus (BP) nanosheets with strong negative charges via mesoporous silica-coated upconversion nanoparticles (UCNPs). Synergistic treatment of photothermal, photodynamic and chemotherapy can be achieved after loading doxorubicin (DOX). The nanocomposites perform excellent antitumor efficiency under 808 nm near-infrared (NIR) light, and avoid the slightly lower efficiency and limited penetration depth of conventional ultraviolet and visible (UV–vis) light. In this system, the pore size of mesoporous silica and the large specific surface area of BP are advantageous for achieving high DOX loading capacity. Furthermore, the reduction in the red/green (R/G) ratio elicited by DOX release can be employed to determine the extent of DOX release by the fluorescence resonance energy transfer (FRET) process. CT/MR imaging induced by doping of rare earth ions imparts multimode imaging capabilities to nanosystem under 808 nm light irradiation, thereby enabling imaging-guided cancer treatment.