Rational Design of All-Organic Nanoplatform for Highly Efficient MR/NIR-II Imaging-Guided Cancer Phototheranostics.

Organic theranostic nanomedicine has precision multimodel imaging capability and concurrent therapeutics under noninvasive imaging guidance. However, the rational design of desirable multifunctional organic theranostics for cancer remains challenging. Rational engineering of organic semiconducting nanomaterials has revealed great potential for cancer theranostics largely owing to their intrinsic diversified biophotonics, easy fabrication of multimodel imaging platform, and desirable biocompatibility. Herein, a novel all-organic nanotheranostic platform (TPATQ-PNP NPs) is developed by exploiting the self-assembly of a semiconducting small molecule (TPATQ) and a new synthetic high-density nitroxide radical-based amphiphilic polymer (PNP). The nitroxide radicals act as metal-free magnetic resonance imaging agent through shortened longitudinal relaxation times, and the semiconducting molecules enable ultralow background second near-infrared (NIR-II, 1000-1700 nm) fluorescence imaging. The as-prepared TPATQ-PNP NPs can light up whole blood vessels of mice and show precision tumor-locating ability with synergistic (MR/NIR-II) imaging modalities. The semiconducting molecules also undergo highly effective photothermal conversion in the NIR region for cancer photothermal therapy guided by complementary tumor diagnosis. The designed multifunctional organic semiconducting self-assembly provides new insights into the development of a new platform for cancer theranostics.

Engineering Oxaliplatin Prodrug Nanoparticles for Second Near-Infrared Fluorescence Imaging-Guided Immunotherapy of Colorectal Cancer.

Colorectal cancer (CRC) ranks as the third common and the fourth lethal cancer type worldwide. Immune checkpoint blockade therapy demonstrates great efficacy in a subset of metastatic CRC patients, but precise activation of the antitumor immune response at the tumor site is still challenging. Here a versatile prodrug nanoparticle for second near-infrared (NIR-II) fluorescence imaging-guided combinatory immunotherapy of CRC is reported. The prodrug nanoparticles are constructed with a polymeric oxaliplatin prodrug (PBOXA) and a donor-spacer-acceptor-spacer-donor type small molecular fluorophore TQTCD. The later displays large Stokes shift (>300 nm), fluorescence emission over 1000 nm, and excellent photothermal conversion performance for NIR-II fluorescence imaging-guided photothermal therapy (PTT). The prodrug nanoparticles show seven times higher intratumoral OXA accumulation than free oxaliplatin. TQTCD-based PTT and PBOXA-induced chemotherapy trigger immunogenic cell death of the tumor cells and elicit antitumor immune response in a spatiotemporally controllable manner. Further combination of the prodrug nanoparticle-based PTT/chemotherapy with programmed death ligand 1 blockade significantly promotes intratumoral infiltration of the cytotoxic T lymphocytes and eradicates the CRC tumors. The NIR-II fluorescence imaging-guided immunotherapy may provide a promising approach for CRC treatment.

Gadolinium-Chelated Conjugated Polymer-Based Nanotheranostics for Photoacoustic/Magnetic Resonance/NIR-II Fluorescence Imaging-Guided Cancer Photothermal Therapy.

Our exploiting versatile multimodal theranostic agent aims to integrate the complementary superiorities of photoacoustic imaging (PAI), second near-infrared (NIR-II, 1000-1700) fluorescence and T1-weighted magnetic resonance imaging (MRI) with an ultimate objective of perfecting cancer diagnosis, thus improving cancer therapy efficacy. Herein, we engineered and prepared a water-soluble gadolinium-chelated conjugated polymer-based theranostic nanomedicine (PFTQ-PEG-Gd NPs) for in vivo tri-mode PA/MR/NIR-II imaging-guided tumor photothermal therapy (PTT). Methods: We firstly constructed a semiconducting polymer composed of low-bandgap donor-acceptor (D-A) which afforded the strong NIR absorption for PAI/PTT and long fluorescence emission to NIR-II region for in vivo imaging. Then, the remaining carboxyl groups of the polymeric NPs could effectively chelate with Gd3+ ions for MRI. The in vitro characteristics of the PFTQ-PEG-Gd NPs were studied and the in vivo multimode imaging as well as anti-tumor efficacy of the NPs was evaluated using 4T1 tumor-bearing mice. Results: The obtained theranostic agent showed excellent chemical and optical stability as well as low biotoxicity. After 24 h of systemic administration using PQTF-PEG-Gd NPs, the tumor sites of living mice exhibited obvious enhancement in PA, NIR-II fluorescence and positive MR signal intensities. Better still, a conspicuous tumor growth restraint was detected under NIR light irradiation after administration of PQTF-PEG-Gd NPs, indicating the efficient photothermal potency of the nano-agent. Conclusion: we triumphantly designed and synthesized a novel and omnipotent semiconducting polymer nanoparticles-based theranostic platform for PAI, NIR-II fluorescence imaging as well as positive MRI-guided tumor PTT in living mice. We expect that such a novel organic nano-platform manifests a great promise for high spatial resolution and deep penetration cancer theranostics.

Polypeptide-Conjugated Second Near-Infrared Organic Fluorophore for Image-Guided Photothermal Therapy.

Image-guided photothermal therapy (PTT) is an attractive strategy to improve the diagnosis accuracy and treatment outcomes by monitoring the accumulation of photothermal agents in tumors in real-time and determining the best treatment window. Taking advantage of the superior imaging quality of NIR-II fluorescence imaging and remote-controllable phototherapy modality of PTT, we developed a facile macromolecular fluorophore (PF) by conjugating a small-molecule NIR-II fluorophore (Flav7) with an amphiphilic polypeptide. The PF can form uniform micelles in aqueous solution, which exhibit a slight negative charge. In vitro experimental results showed that the PF nanoparticles showed satisfactory photophysical properties, prominent photothermal conversion efficiency (42.3%), excellent photothermal stability, negligible cytotoxicity, and photothermal toxicity. Meanwhile, the PF can visualize and feature the tumors by NIR-II fluorescence imaging owing to prolonged blood circulation time and enhanced accumulation in tumors. Moreover, in vivo studies revealed that the PF nanoparticles achieved an excellent photothermal ablation effect on tumors with a low dose of NIR-II dye and light irradiation, and the process can be traced by NIR fluorescence imaging.

Size-Dependent Ag2S Nanodots for Second Near-Infrared Fluorescence/Photoacoustics Imaging and Simultaneous Photothermal Therapy.

Ag2S nanoparticles are increasingly important in biomedicine, such as in cancer imaging. However, there has been only limited success in the exploration of theranostic Ag2S nanoparticles for photoinduced cancer imaging and simultaneous therapy. Here we report size-dependent Ag2S nanodots (NDs) with well-defined nanostructure as a theranostic agent for multimodal imaging and simultaneous photothermal therapy. The NDs are precisely synthesized through carefully controlled growth of Ag2S in hollow human serum albumin nanocages. These NDs produce effective fluorescence in second near-infrared (NIR-II) region, distinct photoacoustic intensity, and good photothermal conversion in a size-dependent manner under light irradiation, thereby generating sufficient in vivo fluorescence and photoacoustic signals as well as potent hyperthermia at tumors. Moreover, Ag2S NDs possess ideal resistance to photobleaching, effective cellular uptake, preferable tumor accumulation, and in vivo elimination, thus facilitating NIR-II fluorescence/photoacoustics imaging with both ultrasensitivity and microscopic spatial resolution and simultaneous photothermal tumor ablation. These findings provide insight into the clinical potential of Ag2S nanodots for cancer theranostics.