Nonspecific Targeting Research Articles

Alicyclobacillus suci produces more guaiacol in media and has duplicate copies of vdcC compared to closely related Alicyclobacillus acidoterrestris.

Microbial spoilage increases food waste. To address that challenge, it is critical to recognize and control those microbial groups with the greatest spoilage potential. Non-specific targeting of broad microbial groups (e.g., the genus of Alicyclobacillus) in which only some members cause food spoilage results in untenable, overly broad interventions. Much of the food industry does not differentiate between guaiacol-producing and non-guaiacol-producing Alicyclobacillus species. This is overly broad because Alicyclobacillus spp. which cannot produce guaiacol can be present in beverages without causing spoilage. Furthermore, no distinction is made between Alicyclobacillus suci and Alicyclobacillus acidoterrestris because A. suci is newly split from A. acidoterrestris and most of the food industry still considers them to be the same. However, these findings indicate that A. suci may have greater spoilage potential than A. acidoterrestris due to differences in their genomic determinants for guaiacol production.

An updated landscape on nanopharmaceutical delivery for mitigation of colon cancer.

Globally, colorectal cancer (CRC) continues to rank among the leading causes of cancer-related death. Systemic toxicity, multidrug resistance, and nonspecific targeting often pose challenges to conventional therapy for CRC. Because it is a complex disease with a complex genetic and environmental pathophysiology, advanced therapeutic strategies are needed. Nanotechnology presents a potential solution that may maximize therapeutic efficacy while minimizing negative effects by enabling personalized delivery of anticancer drugs. This review focuses on recent developments in colorectal drug delivery systems based on nanotechnology. Numerous nanomaterials, including liposomes, dendrimers, micelles, exosomes, and gold nanoparticles, are developed and used. Distinctive characteristics of mentioned nanocarriers are discussed along with strategies that can be employed for enhancing the delivery of drugs to colorectal cancer cells. The review also quotes the most relevant preclinical and clinical studies that show how these nanomaterials improve drug solubility, stability, and targeted delivery while overcoming the shortcomings of conventional therapies. Nanotechnology has made CRC treatment very efficient and advanced, which has opened up new possibilities for targeted drug delivery. Preclinical and clinical studies have also proved that the use of nano-formulations in colon-specific delivery systems have significant results, indicating potential for better patient outcomes. Future research can be done in order to overcome the hurdles regarding biocompatibility, expansion, and regulatory challenges. Large-scale clinical trials and nanomaterial formulation optimization should be the main goals of future research to confirm the efficacy and safety of these novel treatments.

Dual-drug loaded manganese dioxide nanoparticles coated with bacterial outer-membrane vesicles for chemo-immunotherapy in lung cancer

Lung cancer is the most leading cause of cancer death. Traditional chemotherapy has unavoidable drawbacks of nonspecific tumor targeting, high toxicity, and poor therapeutic efficiency. Nanocarriers can achieve accurate delivery and reduce adverse reactions of drugs, which have received extensive attention. In this work, hollow manganese dioxide (HMnO2) nanoparticle (NP) that is highly responsive to tumor microenvironment, was simultaneously loaded with paclitaxel (PTX), a chemotherapy drug, and imiquimod (R837), a toll-like receptor 7 agonist. Those NPs were then coated with bacterial outer-membrane vesicles (OMVs-HMnO2@PTX + R837 NPs), whose surface proteins could act as tumor-specific antigens. The obtained nanovaccine inherited superior tumor-targeting capacity of OMVs and promoted retention in tumors. As a result, intravenous injection of the nanovaccine led to remarkable tumor growth inhibition. Furthermore, we found that the nanovaccine effectively boosted dendritic cells maturation and increased cytotoxic T lymphocytes infiltration. Taken together, these results demonstrated the great potential in applying OMVs-enveloped nano-activator in cancer chemo-immunotherapy.

Beyond aromatherapy: can essential oil loaded nanocarriers revolutionize cancer treatment?

Cancer, a complex global health burden, necessitates the development of innovative therapeutic strategies. While chemotherapy remains the primary treatment approach, its severe side effects and chemoresistance drive the search for novel alternatives. Essential oils (EOs), consisting of diverse bioactive phytochemicals, offer promise as anticancer agents. However, their limitations, such as instability, limited bioavailability, and non-specific targeting, hinder their therapeutic potential. These challenges were circumvented by utilizing nanoparticles and nanosystems as efficient delivery platforms for EOs. This review highlights the accumulating evidence based on loading EOs into several nanocarriers, including polymeric nanoparticles, nanoemulsions, nanofibers, lipid-based nanocapsules and nanostructures, niosomes, and liposomes, as effective anticancer regimens. It covers extraction and chemical composition of EOs, their mechanisms of action, and targeting strategies to various tumors. Additionally, it delves into the diverse landscape of nanocarriers, including their advantages and considerations for cancer targeting and EO encapsulation. The effectiveness of EO-loaded nanocarriers in cancer targeting and treatment is examined, highlighting enhanced cellular uptake, controlled drug release, and improved therapeutic efficacy. Finally, the review addresses existing challenges and future perspectives, emphasizing the potential for clinical translation and personalized medicine approaches.

TRPV1-targeted ion-responsive hydrogel against pyroptosis of dry eye disease

Dry eye disease (DED) is a complex ocular surface abnormality characterized by tear film hyperosmolarity, inflammation, and damage. Left untreated, DED can lead to a self-perpetuating vicious cycle of worsening symptoms. Existing treatments for DED face challenges related to limited drug delivery to the ocular surface and potential side effects from nonspecific drug targeting. In an effort to address these issues, we developed a novel ion-responsive in situ gelling system targeting the transient receptor potential vanilloid 1 (TRPV1), based on co-assembly of the hydrogelator KFQ12 with the functional peptide V1-Cal. The KFQ12/V1-Cal (KVC) aqueous solution, when dripped and mixed with the ionic tear film on the ocular surface, rapidly transformed into a honeycomb-like hydrogel. This hydrogel exhibited prolonged retention on the ocular surface, serving as a stable scaffold for corneal epithelium regeneration and providing protection against external pathogens while maintaining gas exchange. In a murine model of DED, the KVC hydrogel demonstrated superior therapeutic efficacy due to its sustained release characteristics and specific inhibition of the TRPV1 channel activated by hyperosmotic or desiccating stress. By performing transcriptome sequencing and experimental validation both in vivo and in vitro, we confirmed the mechanism of the TRPV1-Ca2+-Pyroptosis axis in the pathogenesis of DED. Our research provides novel perspectives on the understanding and treatment of DED, and introduces a potential ocular surface drug delivery system characterized by superior biosafety, prolonged retention, and improved therapeutic outcomes.

Unveiling The Applications of Nanoparticles in Cancer Immunotherapy

Cancer immunotherapy has proven its potential application by enhancing the capacity of the immune system to destroy cancer cells. However, several challenges, such as non-specific targeting, variability in clinical response, and therapeutic resistance, are associated with immunotherapy, making it less efficacious. Nanoparticles (NPs) as a drug delivery system provide additional advantages during immunotherapy by ensuring targeted delivery of antigens. NPs can also change the cancer environment through adjuvant delivery, forcing cancer cells to be destroyed. Here, several applications of NPs are summarized to help enhance the therapeutic values of immunotherapy through several mechanisms. This article outlines the important developments and possible applications of NPs to fully realize the promise of cancer immunotherapy, which will eventually open the door to more personalized and efficient cancer treatments.

Design of novel and highly selective SARS-CoV-2 main protease inhibitors.

We have synthesized a novel and highly selective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease peptide mimetic inhibitor mimicking the replicase 1ab recognition sequence -Val-Leu-Gln- and utilizing a cysteine selective acyloxymethyl ketone as the electrophilic warhead to target the active site Cys145. Utilizing a constrained cyclic peptide that locks the conformation between the P3 (Val) and P2 (Leu) residues, we identified a highly selective inhibitor that fills the P2 pocket occupied by the leucine residue sidechain of PF-00835231 and the dimethyl-3-azabicyclo-hexane motif in nirmatrelvir (PF-07321332). This strategy resulted in potent and highly selective Mpro inhibitors without inhibiting essential host cathepsin cysteine or serine proteases. The lead prototype compound 1 (MPro IC50 = 230 ± 18 nM) also inhibits the replication of multiple SARS-CoV-2 variants in vitro, including SARS-CoV-2 variants of concern, and can synergize at lower concentrations with the viral RNA polymerase inhibitor, remdesivir, to inhibit replication. It also reduces SARS-CoV-2 replication in SARS-CoV-2 Omicron-infected Syrian golden hamsters without obvious toxicities, demonstrating in vivo efficacy. This novel lead structure provides the basis for optimization of improved agents targeting evolving SARS-CoV-2 drug resistance that can selectively act on Mpro versus host proteases and are less likely to have off-target effects due to non-specific targeting. Developing inhibitors against the active site of the main protease (Mpro), which is highly conserved across coronaviruses, is expected to impart a higher genetic barrier to evolving SARS-CoV-2 drug resistance. Drugs that selectively inhibit the viral Mpro are less likely to have off-target effects warranting efforts to improve this therapy.

Conditional RNA interference in mammalian cells via RNA transactivation

RNA interference (RNAi) is a powerful tool for sequence-specific gene knockdown in therapeutic and research applications. However, spatiotemporal control of RNAi is required to decrease nonspecific targeting, potential toxicity, and allow targeting of essential genes. Herein we describe a class of de-novo-designed RNA switches that enable sequence-specific regulation of RNAi in mammalian cells. Using cis-repressing RNA elements, we engineer RNA devices that only initiate microRNA biogenesis when binding with cognate trigger RNAs. We demonstrate that this conditional RNAi system, termed Orthogonal RNA Interference induced by Trigger RNA (ORIENTR), provides up to 14-fold increases in artificial miRNA biogenesis upon activation in orthogonal libraries. We show that integration of ORIENTR triggers with dCas13d enhances dynamic range to up to 31-fold. We further demonstrate that ORIENTR can be applied to detect endogenous RNA signals and to conditionally knockdown endogenous genes, thus enabling regulatory possibilities including cell-type-specific RNAi and rewiring of transcriptional networks via RNA profile.

Novel Approach for Cardioprotection: In Situ Targeting of Metformin via Conductive Hydrogel System.

Ischemia/reperfusion (I/R) injury following myocardial infarction is a major cause of cardiomyocyte death and impaired cardiac function. Although clinical data show that metformin is effective in repairing cardiac I/R injury, its efficacy is hindered by non-specific targeting during administration, a short half-life, frequent dosing, and potential adverse effects on the liver and kidneys. In recent years, injectable hydrogels have shown substantial potential in overcoming drug delivery challenges and treating myocardial infarction. To this end, we developed a natural polymer hydrogel system comprising methacryloylated chitosan and methacryloylated gelatin modified with polyaniline conductive derivatives. In vitro studies demonstrated that the optimized hydrogel exhibited excellent injectability, biocompatibility, biodegradability, suitable mechanical properties, and electrical conductivity. Incorporating metformin into this hydrogel significantly extended the administration cycle, mitigated mitochondrial damage, decreased abnormal ROS production, and enhanced cardiomyocyte function. Animal experiments indicated that the metformin/hydrogel system reduced arrhythmia incidence, infarct size, and improved cardiac mitochondrial and overall cardiac function, promoting myocardial repair in I/R injury. Overall, the metformin-loaded conductive hydrogel system effectively mitigates mitochondrial oxidative damage and improves cardiomyocyte function, thereby offering a theoretical foundation for the potential application of metformin in cardioprotection.

A polylysine/hyaluronan-based core-shell nanoparticle triggers drug delivery by ATP/hyaluronidase dual stimuli for inducing apoptosis of breast cancer cells

The limitations of self-assembled polymeric nanoparticles for cancer therapy, including instability in the bloodstream, non-specific targeting of cancer cells, and unregulated intracellular drug delivery, were effectively addressed by the development of core-shell SNX@PLL-FPBA/mHA NPs. The core was SNX@PLL-FPBA NPs prepared from polylysine conjugated 3-fluoro-4-carboxyphenylboronic acid (PLL-FPBA) self-assembly and SNX encapsulation, while the shell was methacrylate-modified hyaluronic acid (mHA) adhering to the core by electrostatic interactions and subsequently stabilized by photo-crosslinking, without the use of any organic solvent. SNX@PLL-FPBA/mHA NPs exhibited good stability in varying ionic strengths (0–0.30 M NaCl), pH levels (6.8 and 7.4), and plasma environments mimicking the blood, ensuring their efficacy in systemic circulation. The drug delivery from the nanoparticles was highly sensitive to ATP/Hyals stimuli (82 % within 48 h), closely mimicking the intracellular environment of breast cancer cells. The nanoparticles demonstrated good hemocompatibility and non-toxicity towards human skin fibroblasts. Efficient internalization of SNX@PLL-FPBA/mHA NPs by MCF-7 and MDA-MB-231 breast cancer cells was observed by CLSM and flow cytometry. The intracellular ATP/Hyals stimuli triggered the rapid drug delivery and induced cellular apoptosis. Thus, SNX@PLL-FPBA/mHA NPs were a promising drug nanocarrier for breast cancer therapy, offering improved stability, targeted delivery, and controlled drug release to enhance treatment outcomes.

Recent Advances in Photodynamic Therapy: Metal-Based Nanoparticles as Tools to Improve Cancer Therapy.

Cancer remains a significant global health challenge, with traditional therapies like surgery, chemotherapy, and radiation often accompanied by systemic toxicity and damage to healthy tissues. Despite progress in treatment, these approaches have limitations such as non-specific targeting, systemic toxicity, and resistance development in cancer cells. In recent years, nanotechnology has emerged as a revolutionary frontier in cancer therapy, offering potential solutions to these challenges. Nanoparticles, due to their unique physical and chemical properties, can carry therapeutic payloads, navigate biological barriers, and selectively target cancer cells. Metal-based nanoparticles, in particular, offer unique properties suitable for various therapeutic applications. Recent advancements have focused on the integration of metal-based nanoparticles to enhance the efficacy and precision of photodynamic therapy. Integrating nanotechnology into cancer therapy represents a paradigm shift, enabling the development of strategies with enhanced specificity and reduced off-target effects. This review aims to provide a comprehensive understanding of the pivotal role of metal-based nanoparticles in photodynamic therapy. We explore the mechanisms, biocompatibility, and applications of metal-based nanoparticles in photodynamic therapy, highlighting the challenges and the limitations in their use, as well as the combining of metal-based nanoparticles/photodynamic therapy with other strategies as a synergistic therapeutic approach for cancer treatment.

Enhancing osteoporosis treatment using a targeted, sustained-release drug delivery system based on macrocyclic amphiphile

Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems.

Nanomaterials as a Potential Target for Infectious Parasitic Agents.

Despite the technological advancement in the era of personalized medicine and therapeutics development, infectious parasitic causative agents remain one of the most challenging areas of research and development. The disadvantages of conventional parasitic prevention and control are the emergence of multiple drug resistance as well as the non-specific targeting of intracellular parasites, which results in high dose concentration needs and subsequently intolerable cytotoxicity. Nanotechnology has attracted extensive interest to reduce medication therapy adverse effects including poor bioavailability and drug selectivity. Numerous nanomaterials-based delivery systems have previously been shown in animal models to be effective in the treatment of various parasitic infections. This review discusses a variety of nanomaterials-based antiparasitic procedures and techniques as well as the processes that allow them to be targeted to different parasitic infections. This review focuses on the key prerequisites for creating novel nanotechnology-based carriers as a potential option in parasite management, specifically in the context of human-related pathogenic parasitic agents.

Identification of a mimotope of a complex gp41 Human Immunodeficiency VIrus epitope related to a non-structural protein of Hepacivirus previously implicated in Kawasaki disease.

We have previously isolated a highly mutated VH1-02 antibody termed group C 76-Q13-6F5 (6F5) that targets a conformational epitope on gp41. 6F5 has the capacity to mediate Ab dependent cell cytotoxicity (ADCC). When the VH1-02 group C 76 antibodies variable chain sequence was reverted to germline (76Canc), this still retained ADCC activity. Due to this ability for the 76Canc germline antibody to functionally target this epitope, we sought to identify a protein target for vaccine development. Initially, we interrogated peptide targeting by screening a microarray containing 29,127 linear peptides. Western blot and ELISAs were used to confirm binding and explore human serum targeting. Autoimmune targeting was further interrogated on a yeast-displayed human protein microarray. 76Canc specifically recognized a number of acidic peptides. Meme analysis identified a peptide sequence similar to a non-structural protein of Hepacivirus previously implicated in Kawasaki disease (KD). Binding was confirmed to top peptides, including the Hepacivirus-related and KD-related peptide. On serum competitions studies using samples from children with KD compared to controls, targeting of this epitope showed no specific correlation to having KD. Human protein autoantigen screening was also reassuring. This study identifies a peptide that can mimic the gp41 epitope targeted by 76C group antibodies (i.e. a mimotope). We show little risk of autoimmune targeting including any inflammation similar to KD, implying non-specific targeting of this peptide during KD. Development of such peptides as the basis for vaccination should proceed cautiously.

Targeted Therapy with Cisplatin-Loaded Calcium Citrate Nanoparticles Conjugated with Epidermal Growth Factor for Lung Cancer Treatment.

Lung cancer is the leading cause of cancer-related deaths worldwide with high incidence rates for new cases. Conventional cisplatin (CDDP) therapy has limitations due to severe side effects from nonspecific targeting. To address this challenge, nanomedicine offers targeted therapies. In this study, cisplatin-loaded calcium citrate nanoparticles conjugated with epidermal growth factor (CaCit@CDDP-EGF NPs) were synthesized. The resulting nanodrug had a size below 350 nm with a cation charge. Based on density functional theory (DFT), the CaCit@CDDP NP model containing two citrates substituted on two chlorides exhibited a favorable binding energy of -5.42 eV, and the calculated spectrum at 261 nm closely matched the experimental data. CaCit@CDDP-EGF NPs showed higher inhibition rates against EGFR-expressed and mutant carcinoma cells compared to those of cisplatin while displaying lower cytotoxicity to lung fibroblast cells. Integrating in vitro experiments with in silico studies, these nanoparticles hold promise as a novel nanomedicine for targeted therapy in clinical applications.

Covalent Organic Frameworks as Potential Drug Carriers and Chemotherapeutic Agents for Ovarian Cancers.

Anticancer drugs are often associated with limitations such as poor stability in aqueous solutions, limited cell membrane permeability, nonspecific targeting, and irregular drug release when taken orally. One possible solution to these problems is the use of nanocarriers of drug molecules, particularly those with targeting ability, stimuli-responsive properties, and high drug loading capacity. These nanocarriers can improve drug stability, increase cellular uptake, allow specific targeting of cancer cells, and provide controlled drug release. While improving the therapeutic efficacy of cancer drugs, contemporary researchers also aim to reduce their associated side effects, such that cancer patients are offered with a more effective and targeted treatment strategy. Herein, a set of nine porous covalent organic frameworks (COFs) were tested as drug delivery nanocarriers. Among these, paclitaxel loaded in COF-3 was most effective against the proliferation of ovarian cancer cells. This study highlights the emerging potential of COFs in the field of therapeutic drug delivery. Due to their biocompatibility, these porous COFs provide a viable substrate for controlled drug release, making them attractive candidates for improving drug delivery systems. This work also demonstrates the potential of COFs as efficient drug delivery agents, thereby opening up new opportunities in the field of sarcoma therapy.

Nanosuspensions for improved Cancer Therapy: A Comprehensive Review

Cancer continues to be a major cause of sickness and death in the world's health. Conventional cancer treatments, such radiation and chemotherapy, frequently have drawbacks like poor solubility, limited absorption, and non-specific targeting, which can result in systemic toxicity and decreased efficacy. To get over these restrictions and improve cancer therapy, nanosuspensions—submicron colloidal dispersions of drug particles stabilized by polymers and/or surfactants—have become a viable new approach. This review provides a comprehensive overview of nanosuspensions, including their preparation methods, characterization techniques, and therapeutic applications in cancer treatment. The potential advantages of nanosuspensions over conventional formulations, such as improved solubility, enhanced bioavailability, and tumor-targeted delivery, are discussed in detail. The potential advantages of nanosuspensions over conventional formulations, such as improved solubility, enhanced bioavailability, and tumor-targeted delivery, are discussed in detail. Recent advances in nanosuspension technology, including the development of stimuli-responsive and multifunctional nanosuspensions, are also highlighted. Recent advances in nanosuspension technology, including the development of stimuli-responsive and multifunctional nanosuspensions, are also highlighted. Finally, the challenges and future directions of nanosuspensions in cancer therapy are explored.

Empowering lung cancer treatment: Harnessing the potential of natural phytoconstituent-loaded nanoparticles.

Lung cancer, the second leading cause of cancer-related deaths, accounts for a substantial portion, representing 18.4% of all cancer fatalities. Despite advances in treatment modalities such as chemotherapy, surgery, and immunotherapy, significant challenges persist, including chemoresistance, non-specific targeting, and adverse effects. Consequently, there is an urgent need for innovative therapeutic approaches to overcome these limitations. Natural compounds, particularly phytoconstituents, have emerged as promising candidates due to their potent anticancer properties and relatively low incidence of adverse effects compared to conventional treatments. However, inherent challenges such as poor solubility, rapid metabolism, and enzymatic degradation hinder their clinical utility. To address these obstacles, researchers have increasingly turned to nanotechnology-based drug delivery systems (DDS). Nanocarriers offer several advantages, including enhanced drug stability, prolonged circulation time, and targeted delivery to tumor sites, thereby minimizing off-target effects. By encapsulating phytoconstituents within nanocarriers, researchers aim to optimize their bioavailability and therapeutic efficacy while reducing systemic toxicity. Moreover, the integration of nanotechnology with phytoconstituents allows for a nuanced understanding of the intricate molecular pathways involved in lung cancer pathogenesis. This integrated approach holds promise for modulating key cellular processes implicated in tumor growth and progression. Additionally, by leveraging the synergistic effects of phytoconstituents and nanocarriers, researchers seek to develop tailored therapeutic strategies that maximize efficacy while minimizing adverse effects. In conclusion, the integration of phytoconstituents with nanocarriers represents a promising avenue for advancing lung cancer treatment. This synergistic approach has the potential to revolutionize current therapeutic paradigms by offering targeted, efficient, and minimally toxic interventions. Continued research in this field holds the promise of improving patient outcomes and addressing unmet clinical needs in lung cancer management.

Stem cells derived exosomes as biological nano carriers for VCR sulfate for treating breast cancer stem cells

Due to vincristine sulfate’s (VCR sulfate) toxicity and non-specific targeting, which might adversely damage healthy cells, its clinical application is restricted. In this study, we loaded VCR sulfate on exosomes generated from mesenchymal stem cells (MSCs) to enhance its targeted distribution. Exosomes are able to deliver molecules to specific cells and tissues and have therapeutic potential. In this study, we isolated exosomes from MSCs, and using probe-sonication approach loaded them with VCR sulfate. Using SRB assay, the cytotoxicity of VCR sulfate-Exo was assessed in T47D breast cancer cells, and the results were contrasted with those of free VCR sulfate. Then We labeled markers (CD44+/CD24−) in the cell line to assess the targeting effectiveness of VCR sulfate-Exo using flow cytometry. Our results showed that the cytotoxicity of VCR sulfate-Exo was nearly the same as that of VCR sulfate. Flow cytometry analysis revealed that VRC sulfate-Exo was more effectively targeted to MSCs than free VCR sulfate. Our study shows that loading VCR sulfate to MSCs-derived exosomes can improve their targeted delivery and lessen their side effects. Additional research is required to determine VCR sulfate-Exo’s in vivo effectiveness and safety and improve the loading and delivery strategies.

Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor-acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.