Dual-Engineered Macrophage-Microbe Encapsulation for Metastasis Immunotherapy.

Lung metastases are the leading cause of death among cancer patients. The challenges of inefficient drug delivery, compounded by a robust immunosuppressive microenvironment, make effective treatment difficult. Here, an innovative dual-engineered macrophage-microbe encapsulation (Du-EMME) therapy is developed that integrates modified macrophages and engineered antitumor bacteria. These engineered macrophages, termed R-GEM cells, are designed to express RGD peptides on extracellular membranes, enhancing their tumor cell binding and intratumor enrichment. R-GEM cells are cocultured with attenuated Salmonella typhimurium VNP20009, producing macrophage-microbe encapsulation (R-GEM/VNP cells). The intracellular bacteria maintain bioactivity for more than 24 h, and the bacteria released from R-GEM/VNP cells within the tumor continue to exert bacteria-mediated antitumor effects. This is further supported by macrophage-based chemotaxis and camouflage, which enhance the intratumoral enrichment and biocompatibility of the bacteria. Additionally, R-GEM cells loaded with IFNγ-secreting strains (VNP-IFNγ) form R-GEM/VNP-IFNγ cells. Treatment with these cells effectively halts lung metastatic tumor progression in three mouse models (breast cancer, melanoma, and colorectal cancer). R-GEM/VNP-IFNγ cells vigorously activate the tumor microenvironment, suppressing tumor-promoting M2-type macrophages, MDSCs, and Tregs, and enhancing tumor-antagonizing M1-type macrophages, mature DCs, and Teffs. Du-EMME therapy offers a promising strategy for targeted and enhanced antitumor immunity in treating cancer metastases.

Albumin-Based MUC13 Peptide Nanomedicine Suppresses Liver Cancer Stem Cells via JNK-ERK Signaling Pathway-Mediated Autophagy Inhibition.

Targeting liver cancer stem cells (LCSCs) is a promising strategy for hepatocellular carcinoma (HCC) therapy. Target selection and corresponding inhibitor screening are of vital importance for eliminating the stemness of LCSCs. Peptide-based agents are hopeful but have long been hindered for in vivo application. Herein, we selected a clinically significant target MUC13 and screened out a suitable peptide for preparation of an albumin-based MUC13 peptide nanomedicine, P3@HSA, which suppressed liver cancer stem cells via JNK-ERK signaling pathway-mediated autophagy inhibition. The selected target MUC13 was highly expressed in LCSCs and associated with the prognosis of liver cancer patients. Encouraged by this observation, we screened the corresponding peptide-based inhibitor P3 for further evaluation. P3 could interact with albumin through the intrinsic hydrophobic force and formed the nanomedicine P3@HSA. The prepared nanomedicine could inhibit LCSCs through JNK-ERK signaling pathway-mediated autophagy inhibition and exert potent antitumor effect both in vitro and in vivo. Together, this study provides a promising peptide-based nanomedicine for high-performance HCC treatment.

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to achieve low-toxicity and low-immunogenicity targeted delivery. Signaling pathways related to exosome contents can also be used for safer and more effective immunotherapy against tumors. Exosomes are derived from a wide range of sources, and exhibit different biological characteristics as well as clinical application advantages in different cancer therapies. In this review, we analyzed the main sources of exosomes that have great potential and broad prospects in cancer diagnosis and therapy. Moreover, we compared their therapeutic advantages, providing new ideas for the clinical application of exosomes.

Development of a targeted IL-12 immunotherapy platform for B-cell lymphomas.

Immunotherapy has emerged as a promising approach to cancer treatment that utilizes the potential of the immune system to precisely identify and eradicate cancerous cells. Despite significant progress in immunotherapy, innovative approaches are required to enhance the effectiveness and safety of these treatments. Interleukin-12 (IL-12), widely recognized for its essential function in immune responses, has been explored as a potential candidate for treating cancer. However, early attempts involving the systemic administration of IL-12 were ineffective, with significant adverse effects, thus underscoring the need for innovation. To address these challenges, we developed a therapeutic molecule that utilizes a single-chain IL-12 mutant (IL-12mut) linked to a tumor-targeting arm. Here, we describe the development of a highly effective IL-12-based TMEkine™ platform by employing a B-cell lymphoma model (termed CD20-IL-12mut). CD20-IL-12mut combined the attenuated activities of IL-12 with targeted delivery to the tumor, thereby maximizing therapeutic potential while minimizing off-target effects. Our results revealed that CD20-IL-12mut exhibited potent anticancer activity by inducing complete regression and generating immunological memory for tumor antigens. Collectively, our data provide a basis for additional research on CD20-IL-12mut as a potential treatment choice for patients with B-cell lymphomas such as non-Hodgkin's lymphoma.

From bench to bedside: Platelet biomimetic nanoparticles as a promising carriers for personalized drug delivery.

In recent decades, there has been a burgeoning interest in cell membrane coating strategies as innovative approach for targeted delivery systems in biomedical applications. Platelet membrane-coated nanoparticles (PNPs), in particular, are gaining interest as a new route for targeted therapy due to their advantages over conventional drug therapies. Their stepwise approach blends the capabilities of the natural platelet membrane (PM) with the adaptable nature of manufactured nanomaterials, resulting in a synergistic combination that enhances drug delivery and enables the development of innovative therapeutics. In this context, we present an overview of the latest advancements in designing PNPs with various structures tailored for precise drug delivery. Initially, we describe the types, preparation methods, delivery mechanisms, and specific advantages of PNPs. Next, we focus on three critical applications of PNPs in diseases: vascular disease therapy, cancer treatment, and management of infectious diseases. This review presents our knowledge of PNPs, summarizes their advancements in targeted therapies and discusses the promising potential for clinical translation of PNPs.

In vivo Fate of Targeted Drug Delivery Carriers.

This review aimed to systematically investigate the intracellular and subcellular fate of various types of targeting carriers. Upon entering the body via intravenous injection or other routes, a targeting carrier that can deliver therapeutic agents initiates their journey. If administered intravenously, the carrier initially faces challenges presented by the blood circulation before reaching specific tissues and interacting with cells within the tissue. At the subcellular level, the car2rier undergoes processes, such as drug release, degradation, and metabolism, through specific pathways. While studies on the fate of 13 types of carriers have been relatively conclusive, these studies are incomplete and lack a comprehensive analysis. Furthermore, there are still carriers whose fate remains unclear, underscoring the need for continuous research. This study highlights the importance of comprehending the in vivo and intracellular fate of targeting carriers and provides valuable insights into the operational mechanisms of different carriers within the body. By doing so, researchers can effectively select appropriate carriers and enhance the successful clinical translation of new formulations.

Nowadays, scientists are actively researching nanocarrier drugs. After administration via injection or other methods, these drugs experience in the body and reach the target treatment site to relieve or cure symptoms. As research progresses, scientists are gaining more insights into the behavior of nanocarrier drugs in the body, which is useful in developing safer and more effective drugs. Historically, research has focused primarily on the drug itself. However, it is important to understand that the carrier that delivers and protects the drug (often described as the drug sitting in a "car" or under an "umbrella") plays an essential role in the drug's therapeutic effect. This paper aims to highlight the importance of the carrier's role, which is vital for developing new drugs and advancing basic research.

Exosome for mRNA delivery: strategies and therapeutic applications.

Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications.

Subcellular targeting strategies for protein and peptide delivery.

Cytosolic delivery of proteins and peptides provides opportunities for effective disease treatment, as they can specifically modulate intracellular processes. However, most of protein-based therapeutics only have extracellular targets and are cell-membrane impermeable due to relatively large size and hydrophilicity. The use of organelle-targeting strategy offers great potential to overcome extracellular and cell membrane barriers, and enables localization of protein and peptide therapeutics in the organelles. Although progresses have been made in the recent years, organelle-targeted protein and peptide delivery is still challenging and under exploration. We reviewed recent advances in subcellular targeted delivery of proteins/peptides with a focus on targeting mechanisms and strategies, and highlight recent examples of active and passive organelle-specific protein and peptide delivery systems. This emerging platform could open a new avenue to develop more effective protein and peptide therapeutics.

Bifunctional black phosphorus quantum dots platform: Delivery and remarkable immunotherapy enhancement of STING agonist.

Cancer immunotherapy has been developed to improve therapeutic effects for patients by activating the innate immune stimulator of interferon gene (STING) pathway. However, most patients cannot benefit from this therapy, mainly due to the problems of excessively low immune responses and lack of tumor specificity. Herein, we report a solution to these two problems by developing a bifunctional platform of black phosphorus quantum dots (BPQDs) for STING agonists. Specifically, BPQDs could connect targeted functional groups and regulate surface zeta potential by coordinating metal ions to increase loading (over 5 times) while maintaining high universality (7 STING agonists). The controlled release of STING agonists enabled specific interactions with their proteins, activating the STING pathway and stimulating the secretion release of immunosuppressive factors by phosphorylating TBK1 and IFN-IRF3 and secreting high levels of immunostimulatory cytokines, including IL-6, IFN-α, and IFN-ß. Moreover, the immunotherapy was enhanced was enhanced mild photothermal therapy (PTT) of BPQDs platform, producing enough T cells to eliminate tumors and prevent tumor recurrence. This work facilitates further research on targeted delivery of small-molecule immune drugs to enhance the development of clinical immunotherapy.

Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells.

Targeted therapy remains the future of anti-cancer drug development, owing to the lack of specificity of current treatments which lead to damage in healthy normal tissues. ATR inhibitors have in recent times demonstrated promising clinical potential, and are currently being evaluated in the clinic. However, despite the considerable optimism for clinical success of these inhibitors, reports of associated normal tissues toxicities remain a concern and can compromise their utility. Here, ICT10336 is reported, a newly developed hypoxia-responsive prodrug of ATR inhibitor, AZD6738, which is hypoxia-activated and specifically releases AZD6738 only in hypoxic conditions, in vitro. This hypoxia-selective release of AZD6738 inhibited ATR activation (T1989 and S428 phosphorylation) and subsequently abrogated HIF1a-mediated adaptation of hypoxic cancers cells, thus selectively inducing cell death in 2D and 3D cancer models. Importantly, in normal tissues, ICT10336 is demonstrated to be metabolically stable and less toxic to normal cells than its active parent agent, AZD6738. In addition, ICT10336 exhibited a superior and efficient multicellular penetration ability in 3D tumor models, and selectively eradicated cells at the hypoxic core compared to AZD6738. In summary, the preclinical data demonstrate a new strategy of tumor-targeted delivery of ATR inhibitors with significant potential of enhancing the therapeutic index.

Recent advancements in microspheres mediated targeted delivery for therapeutic interventions in osteoarthritis.

Osteoarthritis (OA), affecting around 240 million people globally is a major threat. Currently, available drugs only treat the symptoms of OA; they cannot reverse the disease's progression. The delivery of drugs to afflicted joints is challenging because of poor vasculature of articular cartilage results in their less bioavailability and quick elimination from the joints. Recently approved drugs such as KGN and IL-1 receptor antagonists also encounter challenges because of inadequate formulations. Therefore, microspheres could be a potential player for the intervention of OA owing to its excellent physicochemical properties. This review primarily focuses on microspheres of distinct biomaterials acting as cargo for drugs and biologicals via different delivery routes in the effective management of OA. Microspheres can improve the efficacy of therapeutics by targeting strategies at specific body locations. This review also highlights clinical trials conducted in the last few decades.

Optimization strategies for mesenchymal stem cell-based analgesia therapy: a promising therapy for pain management.

Pain is a very common and complex medical problem that has a serious impact on individuals' physical and mental health as well as society. Non-steroidal anti-inflammatory drugs and opioids are currently the main drugs used for pain management, but they are not effective in controlling all types of pain, and their long-term use can cause adverse effects that significantly impair patients' quality of life. Mesenchymal stem cells (MSCs) have shown great potential in pain treatment. However, limitations such as the low proliferation rate of MSCs in vitro and low survival rate in vivo restrict their analgesic efficacy and clinical translation. In recent years, researchers have explored various innovative approaches to improve the therapeutic effectiveness of MSCs in pain treatment. This article reviews the latest research progress of MSCs in pain treatment, with a focus on methods to enhance the analgesic efficacy of MSCs, including engineering strategies to optimize the in vitro culture environment of MSCs and to improve the in vivo delivery efficiency of MSCs. We also discuss the unresolved issues to be explored in future MSCs and pain research and the challenges faced by the clinical translation of MSC therapy, aiming to promote the optimization and clinical translation of MSC-based analgesia therapy.

Carrageenan-ferrocene-eicosapentaenoic acid composite hydrogel induce ferroptosis and apoptosis for anti-tumor recurrence and metastasis.

The immune-suppressive microenvironment of solid tumors is a key factor limiting the effectiveness of immunotherapy, which seriously threatens human life and health. Ferroptosis and apoptosis are key cell-death pathways implicated in cancers, which can synergistically activate tumor immune responses. Here, we developed a multifunctional composite hydrogel (CE-Fc-Gel) based on the self-assembly of poloxamer 407, cystamine-linked ιota-carrageenan (CA)-eicosapentaenoic acid (EPA), and ferrocene (Fc). CE-Fc-Gel improved targeting in tumor microenvironment due to its disulfide bonds. Moreover, CE-Fc-Gel promoted lipid peroxidation, enhanced reactive oxygen species (ROS) production, and decreased glutathione peroxidase 4 (GPX4), inducing ferroptosis by the synergistic effect of Fc and EPA. CE-Fc-Gel induced apoptosis and immunogenic cell death (ICD), thereby promoting dendritic cells (DCs) maturation and T cell infiltration. As a result, CE-Fc-Gel significantly inhibited primary and metastatic tumors in vivo. Our findings provide a novel strategy for enhancing tumor immunotherapy by combining apoptosis, ferroptosis, and ICD.

An Endocellulase-Triggered NO Targeted-Release Enzyme-Prodrug Therapy System and Its Application in Ischemia Injury.

Nitric oxide (NO) is a crucial gaseous signaling molecules in regulating cardiovascular, immune, and nervous systems. Controlled and targeted NO delivery is imperative for treating cancer, inflammation, and cardiovascular diseases. Despite various enzyme-prodrug therapy (EPT) systems facilitating controlled NO release, their clinical utility is hindered by nonspecific NO release and undesired metabolic consequence. In this study, a novel EPT system is presented utilizing a cellobioside-diazeniumdiolate (Cel2-NO) prodrug, activated by an endocellulase (Cel5A-h38) derived from the rumen uncultured bacterium of Hu sheep. This system demonstrates nearly complete orthogonality, wherein Cel2-NO prodrug maintains excellent stability under endogenous enzymes. Importantly, Cel5A-h38 efficiently processes the prodrug without recognizing endogenous glycosides. The targeted drug release capability of the system is vividly illustrated through an in vivo near-infrared imaging assay. The precise NO release by this EPT system exhibits significant therapeutic potential in a mouse hindlimb ischemia model, showcasing reductions in ischemic damage, ambulatory impairment, and modulation of inflammatory responses. Concurrently, the system enhances tissue repair and promotes function recovery efficacy. The novel EPT system holds broad applicability for the controlled and targeted delivery of essential drug molecules, providing a potent tool for treating cardiovascular diseases, tumors, and inflammation-related disorders.

Nanotechnology-assisted intracellular delivery of antibody as a precision therapy approach for KRAS-driven tumors.

The Kirsten Rat Sarcoma Virus (KRAS) oncoprotein, one of the most prevalent mutations in cancer, has been deemed undruggable for decades. The hypothesis of this work was that delivering anti-KRAS monoclonal antibody (mAb) at the intracellular level could effectively target the KRAS oncoprotein. To reach this goal, we designed and developed tLyP1-targeted palmitoyl hyaluronate (HAC16)-based nanoassemblies (HANAs) adapted for the association of bevacizumab as a model mAb. Selected candidates with adequate physicochemical properties (below 150 nm, neutral surface charge), and high drug loading capacity (>10%, w/w) were adapted to entrap the antiKRASG12V mAb. The resulting antiKRASG12V-loaded HANAs exhibited a bilayer composed of HAC16 polymer and phosphatidylcholine (PC) enclosing a hydrophilic core, as evidenced by cryogenic-transmission electron microscopy (cryo-TEM) and X-ray photoelectron spectroscopy (XPS). Selected prototypes were found to efficiently engage the target KRASG12V and, inhibit proliferation and colony formation in KRASG12V-mutated lung cancer cell lines. In vivo, a selected formulation exhibited a tumor growth reduction in a pancreatic tumor-bearing mouse model. In brief, this study offers evidence of the potential to use nanotechnology for developing anti-KRAS precision therapy and provides a rational framework for advancing mAb intracellular delivery against intracellular targets.

From structural design to delivery: mRNA therapeutics for cancer immunotherapy.

mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence-known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen-presenting cells (APCs) can synthesize mutant neo-antigens and multi-antigens and present epitopes to T lymphocytes to elicit antitumor effects. In addition, expressing receptors like chimeric antigen receptor (CAR), T-cell receptor (TCR), CD134, and immune-modulating factors including cytokines, interferons, and antibodies in specific cells can enhance immunological response against tumors. With the maturation of in vitro transcription (IVT) technology, large-scale and pure mRNA encoding specific proteins can be synthesized quickly. However, the clinical translation of mRNA-based anticancer strategies is restricted by delivering mRNA into target organs or cells and the inadequate endosomal escape efficiency of mRNA. Recently, there have been some advances in mRNA-based cancer immunotherapy, which can be roughly classified as modifications of the mRNA structure and the development of delivery systems, especially the lipid nanoparticle platforms. In this review, the latest strategies for overcoming the limitations of mRNA-based cancer immunotherapies and the recent advances in delivering mRNA into specific organs and cells are summarized. Challenges and opportunities for clinical applications of mRNA-based cancer immunotherapy are also discussed.

Hair Follicle-Targeted Delivery of Azelaic Acid Micro/Nanocrystals Promote the Treatment of Acne Vulgaris.

Purpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris. Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo. Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy. Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.

Advantages and limitations of nanostructures for biomedical applications.

This review examines recent progress in developing nanoscale drug delivery systems for biomedical applications. Key nanocarriers, including inorganic nanoparticles, dendrimers, protein nanoparticles, polymeric micelles, liposomes, carbon nanotubes (CNTs), quantum dots (QDs), and biopolymeric nanoparticles, were summarized. Compared with free drugs, the tunable physicochemical properties of these materials allow for the encapsulation of therapeutics and improved pharmacokinetics. However, limitations such as toxicity, poor biodegradability, lack of controlled release, and low encapsulation efficiency remain. Inorganic nanoparticles exhibit issues with accumulation and toxicity. Dendrimers require complex syntheses and demonstrations of long-term safety. Protein nanoparticles suffer from low drug loading and stability. Polymeric micelles have stability and tumor penetration limitations. Liposomes exhibit low encapsulation efficiency and rapid clearance. Carbon nanotubes demonstrate toxicity and poor aqueous solubility. Quantum dots contain heavy metals, leading to toxicity. Biopolymeric nanoparticles have low stability and control over release kinetics. Strategies such as surface engineering with polymers and ligands aim to enhance nanoparticle targeting and biocompatibility. The combination of nanostructures in hybrid systems aims to synergize benefits while mitigating individual limitations. Stimulus-responsive and multifunctional nanoparticles enable triggered release and imaging capabilities. Overall, continued research into novel bioinspired designs, smart responsiveness and hybrid approaches is critical to fully realize the clinical potential of engineered nanomedicines for advanced drug delivery applications.

Reprogramming exosomes for immunity-remodeled photodynamic therapy against non-small cell lung cancer.

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2 catalyzes the conversion of H2O2 to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2 to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2 reduces MnO2 to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

A nanocarrier system based on CQDs for efficient mitoxantrone drug delivery.

Cancer is the second most fatal disease among women. In recent years, utilizing strategies based on carbon quantum dots (CQDs) as targeted drug delivery systems has had a significant impact on advancing and improving cancer treatment. This study is focused on the development of a nanocarrier, based on CQDs, for improving the therapeutic efficiency of mitoxantrone (MTX). Hence, the N-doped CQDs were synthesized by a hydrothermal method. Following its purification, MTX was loaded to the CQD, resulting in an increase in the size from 36.78 ± 0.9 nm to 157.8 ± 12.18 nm, with an ideal drug entrapment efficiency of 97 %. Drug release investigation showed a pH-dependent improvement, from 8 % at pH 7.4 to 11 % at pH 5.2 after 48 h. Based on the Methylthiazolyldiphenyl-tetrazolium bromide (MTT) results after 5 h of treatment on MCF-7 breast cancer cells, the N-doped CQD showed no significant effect on the cancer cells, whereas a half maximal Inhibitory Concentration (IC50) was achieved with the N-doped CQD-MTX complex at a concentration between 0.5 to 0.8 µM. Therefore, the newly developed drug delivery complex was capable of providing a rather identical influence on MCF-7 cells, as the free MTX, however, improving the pharmacokinetic of the drug by its controlled and on-target drug release, due to an alteration in distribution and absorption parameters.