Combination of miR159 Mimics and Irinotecan Utilizing Lipid Nanoparticles for Enhanced Treatment of Colorectal Cancer.

Colorectal cancer (CRC) ranks as the third most prevalent global malignancy, marked by significant metastasis and post-surgical recurrence, posing formidable challenges to treatment efficacy. The integration of oligonucleotides with chemotherapeutic drugs emerges as a promising strategy for synergistic CRC therapy. The nanoformulation, lipid nanoparticle (LNP), presents the capability to achieve co-delivery of oligonucleotides and chemotherapeutic drugs for cancer therapy. In this study, we constructed lipid nanoparticles, termed as LNP-I-V by microfluidics to co-deliver oligonucleotides miR159 mimics (VDX05001SI) and irinotecan (IRT), demonstrating effective treatment of CRC both in vitro and in vivo. The LNP-I-V exhibited a particle size of 118.67 ± 1.27 nm, ensuring excellent stability and targeting delivery to tumor tissues, where it was internalized and escaped from the endosome with a pH-sensitive profile. Ultimately, LNP-I-V significantly inhibited CRC growth, extended the survival of tumor-bearing mice, and displayed favorable safety profiles. Thus, LNP-I-V held promise as an innovative platform to combine gene therapy and chemotherapy for improving CRC treatment.

Topochemical-like bandgap regulation engineering: A bismuth thiooxide nanocatalyst for breast cancer phototherapy.

The physical property tuning of nanomaterials is of great importance in energy, medicine, environment, catalysis, and other fields. Topochemical synthesis of nanomaterials can achieve precise control of material properties. Here, we synthesized a kind of element-doped bismuth-based nanomaterial (BOS) by topochemical-like synthesis and used it for the phototherapy of tumors. In this study, we employed bismuth fluoride nanoflowers as a template and fabricated element-doped bismuth oxide nanoflowers by reduction conditions. The product is consistent with the precursor in crystal structure and nanomorphology, realizing topochemical-like synthesis under mild conditions. BOS can generate reactive oxygen species, consume glutathione, and perform photothermal conversion under 730 nm light irradiation. In vitro and in vivo studies demonstrate that BOS could suppress tumor growth by inducing apoptosis and ferroptosis through phototherapy. Therefore, this study offers a general regulation method for tuning the physical properties of nanomaterials by using a topochemical-like synthesis strategy.

Dye-augmented bandgap engineering of a degradable cascade nanoreactor for tumor immune microenvironment-enhanced dynamic phototherapy of breast cancer.

Non-invasive precision tumor dynamic phototherapy has broad application prospects. Traditional semiconductor materials have low photocatalytic activity and low reactive oxygen species (ROS) production rate due to their wide band gap, resulting in unsatisfactory phototherapy efficacy for tumor treatment. Employing the dye-sensitization mechanism can significantly enhance the catalytic activity of the materials. We develop a multifunctional nanoplatform (BZP) by leveraging the benefits of bismuth-based semiconductor nanomaterials. BZP possesses robust ROS generation and remarkable near-infrared photothermal conversion capabilities for improving tumor immune microenvironment and achieving superior phototherapy sensitization. BZP produces highly cytotoxic ROS species via the photocatalytic process and cascade reaction, amplifying the photocatalytic therapy effect. Moreover, the simultaneous photothermal effect during the photocatalytic process facilitates the improvement of therapeutic efficacy. Additionally, BZP-mediated phototherapy can trigger the programmed death of tumor cells, stimulate dendritic cell maturation and T cell activation, modulate the tumor immune microenvironment, and augment the therapeutic effect. Hence, this study demonstrates a promising research paradigm for tumor immune microenvironment-improved phototherapy. STATEMENT OF SIGNIFICANCE: Through the utilization of dye sensitization and rare earth doping techniques, we have successfully developed a biodegradable bismuth-based semiconductor nanocatalyst (BZP). Upon optical excitation, the near-infrared dye incorporated within BZP promptly generates free electrons, which, under the influence of the Fermi energy level, undergo transfer to BiF3 within BZP, thereby facilitating the effective separation of electron-hole pairs and augmenting the catalytic capability for reactive oxygen species (ROS) generation. Furthermore, a cascade reaction mechanism generates highly cytotoxic ROS, which synergistically depletes intracellular glutathione, thereby intensifying oxidative stress. Ultimately, this dual activation strategy, combining oxidative and thermal damage, holds significant potential for tumor immunotherapy.

Topological Regulating Bismuth Nano-Semiconductor for Immunogenic Cell Death-Mediated Sonocatalytic Hyperthermia Therapy.

Immunogenic cell death (ICD) can activate the body's immune system via dead cell antigens to achieve immunotherapy. Currently, small molecule drugs have been used for ICD treatment in clinical, however, how to precisely control the induced ICD while treating tumors is of great significance for improving therapeutic efficacy. Based on this, a sono/light dual response strategy to tumor therapy and activation of ICD is proposed. A topological synthesis method is used to obtain sulfur-doped bismuth oxide Bi2 O3-x Sx (BS) using BiF3 (BF) as a template through reduction and a morphology-controllable bismuth-based nano-semiconductor with a narrow bandgap is constructed. Under the stimulation of ultrasound, BS can produce reactive oxygen species (ROS) through the sonocatalytic process, which cooperates with BS to consume glutathione and enhance cellular oxidative damage, further inducing ICD. Due to the introduction of sulfur in the reduction reaction, BS can achieve photothermal conversion under light, and combine with ROS to treat tumors. Further, with the assistance of ivermectin (IVM) to form composite (BSM), combined with sono/light dual strategy, ICD is promoted and DCs maturation is accelerated. The proposed ICD-mediated hyperthermia/sonocatalytic therapy strategy will pay the way for synergetic enhancement of tumor treatment efficacy and provide a feasible idea for controllable induction of ICD.

Light-Elicited and Oxygen-Saved Iridium Nanocapsule for Oxidative Damage Intensified Oncotherapy.

Regulating redox homeostasis in tumor cells and exploiting oxidative stress to damage tumors is an efficacious strategy for cancer therapy. However, the strengths of organic nanomaterials within this strategy are often ignored. In this work, a light-triggered reactive oxygen species (ROS) damaging nanoamplifier (IrP-T) was developed for enhanced photodynamic therapy (PDT). The IrP-T was fabricated with an amphiphilic iridium complex and a MTH1 inhibitor (TH287). Under green light stimulation, IrP-T catalyzed the oxygen in cells to generate ROS for realizing oxidative damage; meanwhile, TH287 increased the accumulation of 8-oxo-dGTP, further strengthening oxidative stress and inducing cell death. IrP-T could maximize the use of a small amount of oxygen, thus further boosting the efficacy of PDT in hypoxic tumors. The construction of nanocapsules provided a valuable therapeutic strategy for oxidative damage and synergizing PDT.

Recent Developments of Inorganic Nanosensitizers for Sonodynamic Therapy.

As a noninvasive treatment, sonodynamic therapy (SDT) has been widely used in the treatment of tumors because of its ability to penetrate deep tissue with few side effects. As the key factor of SDT, it is meaningful to design and synthesize efficient sonosensitizers. Compared with organic sonosensitizers, inorganic sonosensitizers can be easily excited by ultrasound. In addition, inorganic sonosensitizers with stable properties, good dispersion, and long blood circulation time, have great development potential in SDT. This review summarizes possible mechanisms of SDT (sonoexcitation and ultrasonic cavitation) in detail. Based on these mechanisms, the design and synthesis of inorganic nanosonosensitizers can be divided into three categories: traditional inorganic semiconductor sonosensitizers, enhanced inorganic semiconductor sonosensitizers, and cavitation-enhanced sonosensitizers. Subsequently, the current efficient construction methods of sonosensitizers are summarized including accelerated semiconductor charge separation and enhanced production of reactive oxygen species through ultrasonic cavitation. Furthermore, the advantages and disadvantages of different inorganic sonosensitizers and detailed strategies are systematically discussed on how to enhance SDT. Hopefully, this review could provide new insights into the design and synthesis of efficient inorganic nano-sonosensitizers for SDT.

Protoporphyrin-sensitized degradable bismuth nanoformulations for enhanced sonodynamic oncotherapy.

Decreasing the scavenging capacity of reactive oxygen species (ROS) and enhancing ROS production are the two principal objectives in the development of novel sonosensitizers for sonodynamic therapy (SDT). Herein, we designed a protoporphyrin-sensitized bismuth-based semiconductor (P-NBOF) as a sonosensitizer to generate ROS and synergistically depleted glutathione for enhanced SDT against tumors. The bismuth-based nanomaterial (NBOF) is a wide-bandgap semiconductor. Sensitization by protoporphyrin made it easier to excite electrons under ultrasonic stimulation, and the energy of the lowest unoccupied electron orbital in protoporphyrin was higher than the conduction-band energy of NBOF. Under ultrasound excitation, the excited electrons in the protoporphyrin were injected into the conduction band of the NBOF, increasing its reducing ability leading to the production of more superoxide anion radicals and also helping to increase the charge separation of protoporphyrin leading to the production of more singlet oxygen. Meanwhile, P-NBOF continuously depleted glutathione, which was not only conducive to breaking the redox balance of the tumor microenvironment to enhance the therapeutic efficacy of SDT, but also promoted its degradation and metabolism. The construction of this P-NBOF sonosensitizer thus provided an effective strategy to enhance SDT for tumors. STATEMENT OF SIGNIFICANCE: To enhance the efficacy of sonodynamic tumor therapy, we developed a degradable protoporphyrin-sensitized bismuth-based nano-semiconductor (P-NBOF) by optimizing the band structure and glutathione-depletion ability. Protoporphyrin in P-NBOF under excitation preferentially generates free electrons, which are then injected into the conduction band of NBOF, improving the reducing ability of NBOF and promoting the separation of electron-hole pairs, thereby enhancing the production capacity of reactive oxygen species. Furthermore, P-NBOF can deplete glutathione, reduce the scavenging of reactive oxygen species, and reactivate and amplify the effect of sonodynamic therapy. The construction of the nanotherapeutic platform provides an option for enhancing sonodynamic therapy.