Biomimetic Copper-Doped Polypyrrole Nanoparticles for Enhanced Cancer Low-Temperature Photothermal Therapy.

Introduction: Photothermal therapy (PTT) has a significant potential for its application in precision tumour therapy. However, PTT-induced hyperthermia may damage healthy tissues and trigger the expression of heat shock proteins (HSPs), thereby compromising the long-term therapeutic efficacy of PTT. Methods: In this study, a biomimetic drug delivery system comprising CuP nanozymes as the inner core and platelet membrane (PM) as the outer shell was successfully developed for administering synergistic chemodynamic therapy and mild PTT. PM is encapsulated on CuP to form this biomimetic nanoparticle (PM-coated CuP nanoparticles, PC). PC possesses peroxidase (POD) activity, can facilitate the conversion of hydrogen peroxide into ·OH, thereby inhibiting the expression of HSPs. Results: Upon exposure to low-power laser irradiation (0.5 W/cm2, 1064 nm), PC can convert near-infrared II laser energy into heat energy, thereby enabling the administration of enhanced mild PTT. In vitro and in vivo experiments have demonstrated that this synergistic approach can induce over 90% tumour eradication with favourable biocompatibility. Discussion: PC exhibits high efficacy and biocompatibility, making it a promising candidate for future applications.

Delivery of manganese carbonyl to the tumor microenvironment using Tumor-Derived exosomes for cancer gas therapy and low dose radiotherapy.

The development of novel radiosensitizer with high selectivity and controllability is highly desirable. CO gas could cause damage to mitochondria and thus enhance RT effect. Controlled delivery of CO in tumor is important both to achieve high-efficiency of CO gas therapy and to decrease the risk of CO poisoning. In this study, manganese carbonyl (MnCO) loaded exosome nano-vesicles (MMV) to overcome this conundrum for tumor therapy is developed. After administration, MMV showed its admirable performance in active tumor-targeting, mitochondria damage and radiosensitization therapy. These MMV nanoparticles were able to facilitate robust CO evolution and consequent ROS generation in response to X-ray irradiation both in vitro and in vivo. Significantly, MMV could facilitate a 90% inhibition effect of tumor growth under very low dose (only 2Gy) RT, which is better than high dose (6Gy) radiotherapy. Overall, this study highlights a novel and practical approach to enhancing the efficacy of tumor RT, underscoring the value of future research in the field of CO medicine.

Rapid synthesis of a Bi@ZIF-8 composite nanomaterial as a near-infrared-II (NIR-II) photothermal agent for the low-temperature photothermal therapy of hepatocellular carcinoma.

Hepatocellular carcinoma is the fourth leading cause of cancer-related deaths globally. Advanced nanomaterials have emerged as effective approaches to liver cancer therapy such as photothermal therapy. However, limited penetration depth of photothermal agents (PTAs) activated in the NIR-I bio-window and thermoresistance due to heat shock proteins restrict the therapeutic efficacy of PTT in HCC. Herein, we prepared a Bi@ZIF-8 (BZ) nanomaterial by a simple one-step reduction method. Then, gambogic acid, a natural inhibitor of Hsp90, was efficiently loaded onto the BZ nanomaterial via physical mixing. The characterization of the nanomaterial and release of GA due to pH change or NIR-light irradiation were separately studied. Photothermal conversion efficiency was calculated, and therapeutic studies were carried out in vitro and in vivo. This nanomaterial exhibited a significantly enhanced drug release rate when the temperature was increased under acidic conditions and had good light stability under laser irradiation and a photothermal conversion efficiency of about 24.4%. In addition, this novel nanomaterial achieved good therapeutic effects with less toxicity in vitro. The BZ nanomaterial loaded with GA caused tumor shrinkage as well as disappearance and effectively downregulated Hsp90 expression in tumors in vivo. Moreover, this novel nanomaterial exhibited good biocompatibility and potential for application in low-temperature PTT with excellent tumor destruction efficacy.

Stellate Plasmonic Exosomes for Penetrative Targeting Tumor NIR-II Thermo-Radiotherapy.

Multifunctional gold (Au)-based nanomaterials with high atomic number (symbol Z) and strong absorbance in the second near-infrared window (NIR-II) property are emerging as promising candidates for tumor thermo-radiotherapy. The main limitations of applying Au-based nanomaterials to biomedical studies include the absence of active tumor-targeting ability, penetrating efficiency, and stability. In this study, we present a novel type of tumor cell-derived stellate plasmonic exosomes (TDSP-Exos) for penetrative targeted tumor NIR-II thermo-radiotherapy and photoacoustic imaging. The TDSP-Exos are abundantly and easily produced by the incubation of tumor cells with gold nanostars, based on which gold nanostars promote the exocytosis of exosomes from tumor cells. Compared with bare gold nanostars, the TDSP-Exos exhibit pronounced accumulation in deep tumor tissues and perform well in both PA imaging and NIR-II thermo-radiotherapy against the tumor. Moreover, the TDSP-Exos improve tumor hypoxia to enhanced radiotherapy by NIR-II photothermal therapy. This work indicates that the tumor cell-derived exosomes have the potential to function as a universal carrier of photothermal agents for targeted tumor NIR-II thermo-radiotherapy.

Enhanced Tumor Targeting and Radiotherapy by Quercetin Loaded Biomimetic Nanoparticles.

In Chinese traditional medicine, quercetin (QT) plays a fundamental role in the treatment of asthma, as an anti-allergen and to lower blood pressure. Recent evidence suggests that QT can improve tumor radiosensitivity through multiple mechanisms. However, poor tumor tissue targeting ability and low water solubility of QT limit its usefulness in the treatment of cancers. Herein, we designed a novel drug delivery system (CQM) consisting of inner QT loaded mesoporous silica nanoparticles (MSNs) and outer cancer cell membranes (CM). The developed nanoplatform had strong anti-cancer effects under X-ray irradiation and good QT loading characteristics. In addition, CQM effectively targeted tumor tissues. Results of in vitro and in vivo experiments demonstrated that the developed CQM drug delivery system has excellent tumor targeting ability and effectively inhibited tumor growth. Therefore, the CQM platform realized targeted drug delivery and radiotherapy sensitization, which provided a newfangled idea of cancer treatment.

Cancer cell membrane-camouflaged MOF nanoparticles for a potent dihydroartemisinin-based hepatocellular carcinoma therapy.

Developing new drugs for cancer treatment remains a challenging task. Herein, cancer cell membrane biomimetic ferrous ion-doped metal-organic framework nanoparticles (ZIF-8 nanoparticles) combined with dihydroartemisinin (DHA) have been designed for targeted cancer treatment with low toxicity and side effects. The biomimetic nanomaterials (CDZs) have excellent homologous targeting ability and can accumulate in tumor tissues. In an acid tumor microenvironment, ferrous ions and DHA could be released with the degradation of materials. DHA, an ancient Chinese medicine, combines with ferrous ions to produce a powerful anti-tumor effect. In human liver cancer models, about 90.8% of tumor growth was suppressed. In addition, the nanomaterial has no obvious toxic and side effects in vivo and is a highly effective and low-toxicity anti-tumor drug with a strong clinical application value.

Bimetallic nanodots for tri-modal CT/MRI/PA imaging and hypoxia-resistant thermoradiotherapy in the NIR-II biological windows.

Hypoxic tumor microenvironment leads to resistance or failure of radiotherapy (RT). As a non-invasive therapy, photothermal therapy (PTT) can improve the tumor hypoxic microenvironment in addition to directly killing tumor cells. PTT combined with RT (thermoradiotherapy) becomes an emerging treatment. Multi-functional nanoparticles used for hypoxia-resistant thermoradiotherapy in the second near-infrared (NIR-II) biological windows (1000-1700 nm) are urgently needed to be developed. Here, a facil method synthesis of ultra-small cysteamine (Cys)-coated FePd bimetallic nanodots (NDs) is reported. These NDs can not only produce effective hyperthermia (35.4%) when irradiated in the NIR-II region (1064 nm) but also have an enhanced radiation effect due to i) Hypoxic improvement in tumor tissues by photothermal treatment in the NIR-II Biological Windows can greatly enhance the sensitivity of tumor cells to radiotherapy ii) The ability of NDs to deposit radiation energy in tumors has further enhanced the sensitivity of tumor cells to radiotherapy. Meanwhile, NDs was a contrast agent for tri-modal imaging including computed tomography (CT)/magnetic resonance imaging (MRI)/photoacoustic imaging (PAI) in vitro and in vivo. Both in vitro and in vivo tests demonstrated good biocompatibility and excellent stability of NDs, indicating great potential for clinical applications.