Injectable Ovalbumin-Based Composite Implant for Photothermal Tumor Therapy.

Polymeric hydrogels with three-dimensional network structures have found tremendous applications in biomedicine. Herein, we report the synthesis of a multifunctional implant based on ovalbumin (OVA) as a carrier capable of synergistically delivering a photothermal transducing agent (polydopamine, PDA) to tumors. The formation of PDA was achieved by utilizing the basicity of OVA, whereas the formation of the hydrogel implant was achieved through the in vitro/in vivo near-infrared (NIR) laser-induced hyperthermia of PDA. The as-prepared PDA@OVA implant exhibits high photothermal conversion efficiency (38.7 %). Once implanted in vivo, the OVA-based implant shows great versatility in the treatment of malignant tumors. Furthermore, a chemotherapeutic (doxorubicin, DOX) and a contrast agent (iohexol), dispersed in the OVA solution in advance, can also be firmly entrapped in the hydrogel along with the hydrogel formation. It is anticipated that the multifunctional OVA-based implant, not showing any obvious toxicity to healthy tissue, could be a promising system for synergistic cancer treatment.

Photonic Hyperthermia Synergizes with Immune-Activators to Augment Tumor-Localized Immunotherapy.

Photothermal immunotherapy, the combination of photothermal hyperthermia and immunotherapy, is a noninvasive and desirable therapeutic strategy to address the deficiency of traditional photothermal ablation for tumor treatment. However, insufficient T-cell activation following photothermal treatment is a bottleneck to achieve satisfactory therapeutic effectiveness. In this work, a multifunctional nanoplatform is rationally designed and engineered on the basis of polypyrrole-based magnetic nanomedicine modified by T-cell activators of anti-CD3 and anti-CD28 monoclonal antibodies, which have achieved robust near infrared laser-triggered photothermal ablation and long-lasting T-cell activation, realizing diagnostic imaging-guided immunosuppressive tumor microenvironment regulation following photothermal hyperthermia by reinvigorating tumor-infiltrating lymphocytes. By virtue of high-efficient immunogenic cell death and dendritic cell maturation combined with T-cell activation, this nanosystem markedly restrains primary and abscopal tumors as well as metastatic tumors with negligible side effects in vivo, exerting the specific function for suppressing tumor recurrence and metastasis by establishing a long-term memory immune response.

Synthesis of a Clay-Based Nanoagent for Photonanomedicine.

Photo-induced cancer therapies, mainly including photothermal therapy (PTT) and photodynamic therapy (PDT), have attracted numerous attentions owing to the high selectivity, convenience, and few side effects. However, single PTT usually requires high laser power density, and single PDT usually needs a high photosensitizer dosage. Herein, a kind of composite nanocarrier based on clay (laponite)-polypyrrole (LP) nanodisks was synthesized via the in situ polymerization of pyrrole in the interlayer space of laponite. LP composite nanodisks were then coated with polyvinylpyrrolidone (PVP) to form the LP-PVP (LPP) composite nanodisks which show an excellent colloidal stability and in vitro and in vivo biocompatibility. The interlayer space of LPP can be further used for the loading of Chlorin e6 (Ce6), with an ultrahigh loading capacity of about 89.2%. Furthermore, the LPP nanocarrier can enhance the PDT effect of Ce6 under the irradiation of a 660 nm laser, through enhancing its solubility and cellular uptake amount. Besides, it was found that LPP nanodisks exhibit a more outstanding photothermal performance under a 980 nm near-infrared laser (NIR) than a 808 nm NIR laser, with the photothermal conversion efficiency of 45.7 and 27.7%, respectively. The in vitro and in vivo tumor therapy results evidently confirm that the Ce6-loaded LPP nanodisks have a combined tumor PTT and PDT effect, which can significantly suppress the tumor malignant proliferation.

Preparation of injectable temperature-sensitive chitosan-based hydrogel for combined hyperthermia and chemotherapy of colon cancer.

The purpose of this study was to design an injectable hydrogel with temperature-sensitive property for safe and high efficient in vivo colon cancer hyperthermia and chemotherapy. Chitosan (CS) solution was injected into the tumor at room temperature and automatically gelled after warming to body temperature in the present of ß-glycerophosphate (ß-GP). Combined localized tumor photothermal and chemotherapy were achieved by dissolving photothermal material MoS2/Bi2S3-PEG (MBP) nanosheets and drug molecule doxorubicin (DOX) into the hydrogel, and the gel system could encapsulate DOX and MBP nanosheets and prevent them from entering the blood circulation and damaging normal tissues and cells. More importantly, the CS/MBP/DOX (CMD) hydrogel exhibited a photothermal efficiency of 22.18% and 31.42% in the first and second near infrared light (NIR I and NIR II) biowindows respectively at a low MBP concentration (0.5 mg/mL). Besides, the release of the DOX from CMD hydrogel was controllable since the gel temperature could be governed by NIR laser irradiation. Moreover, the chitosan-based hydrogel had antibacterial effects. The designed composite hydrogel is anticipated to act as a platform for the high efficient treatment of tumors owing to the different penetration depths of NIR I and NIR II.

One-pot synthesis of polypyrrole nanoparticles with tunable photothermal conversion and drug loading capacity.

With an excellent near-infrared (NIR) light-responsive property, polypyrrole (PPy) nanoparticle has emerged as a promising NIR photothermal transducing agent for tumor photothermal therapy (PTT). Herein, we reported the PVP mediated one-pot synthesis of colloidal stable and biocompatible PPy nanoparticles (PPy-PVP NPs) for combined tumor photothermal-chemotherapy. The influence of molecular weight and PVP concentration on the spectroscopic characteristic, photothermal feature, drug loading performance, and antitumor efficiency of the resultant PPy-PVP NPs was systematically studied. By choosing PVP with a molecular weight of 360 kDa (concentration of 5 mg/mL) as the template and surface modifier during the synthesis, PPy-PVP NPs with optimal spectroscopic characteristic, photothermal feature, drug loading performance, and antitumor efficiency were synthesized. Findings in this study are anticipated to provide an in-depth understanding of the important character of surface engineering in the rational design and biomedical applications of PPy NPs.

Preparation of Poly(lactic-co-glycolic acid)-Based Composite Microfibers for Postoperative Treatment of Tumor in NIR I and NIR II Biowindows.

In this work, a novel kind of electrospun microfiber to deliver a photothermal agent and an anticancer drug to tumor sites is explored. Photothermal therapy agent (MoS2 nanosheets) and doxorubicin (DOX) are incorporated with poly(lactic-co-glycolic acid) (PLGA) microfiber via electrospinning a solution of PLGA, MoS2 , and DOX. The designed microfiber with uniform fibrous morphology and negligible in vitro/in vivo hemo-/histo-toxicity is used as a durable photothermal agent, which shows an excellent photothermal transform ability and acceptable photothermal stability in both the first and second near-infrared light (NIR I and II) biowindows. The synergistic in vivo tumor chemotherapy and photothermal therapy efficiency of the composite microfibers are studied in postoperative treatment of cancer. It is found that the tumor postoperative reoccurrence can be completely prohibited owing to the synergistic tumor therapy efficiency in both the NIR I and NIR II biowindows.

Fe3+-Induced Synchronous Formation of Composite Hydrogels for Effective Synergistic Tumor Therapy in NIR-I/II Biowindows.

Alginate-Ca2+ hydrogel has been used to immobilize photothermal materials as well as chemotherapy drugs at lesion sites to prevent their entry into the bloodstream. However, the alginate-Ca2+ gelation mechanism may result in hardening of the blood vessels because of Ca2+ migration to the lesion site. In this study, a unique and facile one-pot formation of chemotherapeutic (doxorubicin, DOX) and polypyrrole-containing alginate hydrogel was designed by introducing Fe3+, which can synchronously induce the polymerization of pyrrole and gelatinization of alginate, into the DOX/pyrrole/alginate solution. The formed composite hydrogel was endowed with superior photothermal conversion properties in both the NIR-I (650-950 nm) and NIR-II (1000-1700 nm) biowindows and light-to-heat conversion efficiency higher than 50%, which enabled effective tumor hyperthermia treatment. Besides, near-infrared (NIR) irradiation could be used as a remote controller to trigger the DOX-release because of the heat generation, thus achieving continuous and on-demand tumor chemotherapy. The composite polymer hydrogels exhibited favorable hemo-, cyto-, and histocompatibility, as well as simple and cost-effective preparation and good clinical prospects.

Design of injectable agar-based composite hydrogel for multi-mode tumor therapy.

We designed an injectable hydrogel by dissolving MoS2/Bi2S3-PEG (MBP), doxorubicin (DOX) and agar into water for the concurrent tumor photothermal and chemotherapy. The formed solution was able to be intra-tumorally (I.T.) administered into tumor at a relatively high temperature and automatically formed a hydrogel after cooling to body temperature. The resultant Agar/MBP/DOX (AMD) hydrogel can act as a macro-vessel to retain the MBP nanosheet and DOX and restrict their access to body fluid circulation. Moreover, AMD hydrogel did not compromise the photoacoustic and computed tomography imaging capacity, as well as the photothermal and chemotherapy efficiency of MBP nanosheets and DOX. The heat from the photothermal transformation of MBP nanosheet can promote the drug-release from the hydrogel and thus enable an on-demand drug release. Furthermore, antibiotics were also able to be encapsulated in the hydrogel to avoid the potential wound infection during tumor surgery.

Bottom-up synthesis of WS2 nanosheets with synchronous surface modification for imaging guided tumor regression.

Two-dimensional transition metal dichalcogenides (TMDs) have been receiving great attention as NIR photothermal transducing agent in tumor photothermal therapy. Keeping in mind the low efficiency of the conventional top-down exfoliated 2D TMDs and the complexity of their surface modifications, we herein proposed a bottom-up strategy for the one-pot hydrothermal and controlled synthesis of surface polyvinyl pyrrolidone (PVP) modified WS2 nanosheets. The material design was based on the chelating-coordinating effect between the lone pair electrons of oxygen of PVP carbonyl group and the unoccupied orbital (5d orbitals) of tungsten. The WS2 nanosheets with synchronous surface PVP grafting showed an excellent photothermal conversion performance, while the surface anchored PVP guaranteed its colloidal stability. Moreover, the strong X-ray attenuation ability and near-infrared (NIR) absorbance of WS2-PVP360kDa enabled the sensitive in vitro and in vivo computed tomography and photoacoustic imaging. The WS2-PVP360kDa nanosheets were biocompatible and exhibited promising in vitro and in vivo anti-cancer efficacy. Findings in this report may greatly promote the design of colloidal stable and biocompatible 2D TMDs and their future clinical translations. STATEMENT OF SIGNIFICANCE: A bottom-up strategy for the one-pot and controlled synthesis of surface polyvinyl pyrrolidone (PVP) modified WS2 nanosheets was proposed for the first time. By hydrothermally treating the mixture solution of tetrathiotungstate and PVP, Owing to the chelating-coordinating effect between the lone pair electrons of oxygen of PVP carbonyl group and the unoccupied orbital (5d orbitals) of tungsten, PVP was synchronously graphed on WS2-PVP nanosheets surface. The formed WS2-PVP nanosheets were colloidal stable, biocompatible, and exhibited promising computed tomography, photoacoustic imaging and tumor photothermal therapy efficacy both in vitro and in vivo.