Smart Nanocarriers Research Articles

Comprehensive insights into glioblastoma multiforme: drug delivery challenges and multimodal treatment strategies.

Glioblastoma multiforme (GBM) is one of the most common and malignant brain tumors, with a high prevalence in elderly population. Most chemotherapeutic agents fail to reach the tumor site due to various challenges. However, smart nanocarriers have demonstrated excellent drug-loading capabilities, enabling them to cross the blood brain tumor barrier for the GBM treatment. Surface modification of nanocarriers has significantly enhanced their potential for targeting therapeutics. Moreover, recent innovations in drug therapies, such as the incorporation of theranostic agents in nanocarriers and antibody-drug conjugates, have offered newer insights for both diagnosis and treatment. This review focuses on recent advances in new therapeutic interventions for GBM, with an emphasis on the nanotheranostics systems to maximize therapeutic and diagnostic outcomes.

Mitigating the skin phototoxicity of sonodynamic therapy via singlet oxygen-consuming metal-organic frameworks

Sonodynamic anti-cancer therapy relies on the highly active singlet oxygen to induce potent cell death. However, the non-specific biodistribution of sonosensitizers post systemic administration results in a significant accumulation in the skin, and hence the daylight-induced phototoxicity. Here, we report a smart metal-organic framework-based nanocarrier with titanium dioxide (TiO2) as the sonosensitizer for reduced phototoxicity in the skin. The organic ligand bears the imidazole moiety that can facilely consume singlet oxygen in the skin without compromising the anti-cancer efficacy. The reaction between imidazole moiety and singlet oxygen was confirmed by the density functional theory (DFT). Upon light irradiation, the nanocarrier can significantly reduce the phototoxicity post light irradiation in a range of normal cells in vitro and in a mouse model in vivo. Meanwhile, the ligand contains a disulfide moiety that can deplete glutathione and orchestrate the singlet oxygen-induced toxicity in the CT-26 colon cancer cells. As a result, the nanocarrier showed superior in vivo antitumor efficacy in a CT-26 tumor-bearing mice model, leading to significant suppression of tumor growth and improved animal survival rates. The current work provides a tailored nanoscale particle engineering approach to simultaneously minimize phototoxicity in the skin and sensitize sonodynamic anti-cancer therapy.

Synergistic Potential of Nanomedicine in Prostate Cancer Immunotherapy: Breakthroughs and Prospects.

Given the global prevalence of prostate cancer in men, it is crucial to explore more effective treatment strategies. Recently, immunotherapy has emerged as a promising cancer treatment due to its unique mechanism of action and potential long-term effectiveness. However, its limited efficacy in prostate cancer has prompted renewed interest in developing strategies to improve immunotherapy outcomes. Nanomedicine offers a novel perspective on cancer treatment with its unique size effects and surface properties. By employing targeted delivery, controlled release, and enhanced immunogenicity, nanoparticles can be synergized with nanomedicine platforms to amplify the effectiveness of immunotherapy in treating prostate cancer. Simultaneously, nanotechnology can address the limitations of immunotherapy and the challenges of immune escape and tumor microenvironment regulation. Additionally, the synergistic effects of combining nanomedicine with other therapies offer promising clinical outcomes. Innovative applications of nanomedicine include smart nanocarriers, stimulus-responsive systems, and precision medicine approaches to overcome translational obstacles in prostate cancer immunotherapy. This review highlights the transformative potential of nanomedicine in enhancing prostate cancer immunotherapy and emphasizes the need for interdisciplinary collaboration to drive research and clinical applications forward.

Therapeutic delivery of siRNA for the management of breast cancer and triple-negative breast cancer.

Breast cancer is the leading cause of cancer-related deaths among women globally. The difficulties with anticancer medications, such as ineffective targeting, larger doses, toxicity to healthy cells and side effects, have prompted attention to alternate approaches to address these difficulties. RNA interference by small interfering RNA (siRNA) is one such tactic. When compared with chemotherapy, siRNA has several advantages, including the ability to quickly modify and suppress the expression of the target gene and display superior efficacy and safety. However, there are known challenges and hurdles that limits their clinical translation. Decomposition by endonucleases, renal clearance, hydrophilicity, negative surface charge, short half-life and off-target effects of naked siRNA are obstacles that hinder the desired biological activity of naked siRNA. Nanoparticulate systems such as polymeric, lipid, lipid-polymeric, metallic, mesoporous silica nanoparticles and several other nanocarriers were used for effective delivery of siRNA and to knock down genes involved in breast cancer and triple-negative breast cancer. The focus of this review is to provide a comprehensive picture of various strategies utilized for delivering siRNA, such as combinatorial delivery, development of modified nanoparticles, smart nanocarriers and nanocarriers that target angiogenesis, cancer stem cells and metastasis of breast cancer.

Exploring the interaction of Cu-modified B12N12 nanocages for Favipiravir drug delivery using density functional theory study

Drug delivery has become a pivotal strategy in medical research, aiming for precise delivery near cells while minimizing unwanted effects. In this study, we have used density functional theory (DFT) calculations at the B3LYP/6-311G(d,p) basis set to explore the potential of Cu-modified boron nitride (B12N12) nanocages as smart nanocarriers for delivering the Favipiravir (FAV) drug. This study examined the adsorption energy, electronic features, and thermodynamic properties (ΔG and ΔH) of FAV with B12N12 and Cu-modified B12N12 nanocages, revealing enhanced drug-delivery capacity with notable physisorption and negative adsorption energies. A comprehensive analysis confirmed FAV’s interaction with Cu-modified B12N12 nanocages, involving frontier molecular orbitals, adsorption energy, fractional charge transfer, molecular electrostatic potential (MEP), non-covalent interaction (NCI), and natural bond orbital (NBO) assessments. The analyses of frontier molecular orbitals (FMO), partial density of states (PDOS), and natural bond orbital (NBO) indicate that nanocages act as charge acceptors, while the drug acts as a charge donor during the adsorption process. Among the various Cu-modified B12N12 nanocages studied, Cu-doped CuB11N12 emerged as the most promising candidate for transporting FAV, showcasing notably moderate recovery time (ranging from 29.01 ms to 7.25 s at 298.15 K). Remarkably, the CuB11N12 system exhibited exceptional electronic sensitivity (ΔEgap = 65.38 %) to the FAV drug, surpassing other modified systems. Among the modified cases, the Cu-decorated Cu@b64 and Cu@b66 nanocages showed the most significant decrease in energy levels before and after FAV absorption, reducing from 3.28 eV and 3.33 eV to 1.54 eV and 1.59 eV, respectively. This elucidation may lay the foundation for developing effective drug-delivery systems using nanocages for targeted therapies. In conclusion, this study offers a comprehensive insight into the interaction mechanism between the FAV drug and B12N12, unveiling the potential of Cu-modified B12N12 nanocages as promising candidates for delivering the FAV drug.

Nanotechnology in Malaria Treatment: Targeted Drug Delivery Systems and Future Applications

Malaria continued to be a major global health challenge, particularly in regions with high disease burden, despite advancements in treatment options such as Artemisinin-based Combination Therapies (ACTs). The emergence of nanotechnology offered a transformative approach to malaria treatment, with its potential to improve drug delivery, bioavailability, and therapeutic outcomes. This review examined the current applications and advancements in nanotechnology for malaria treatment, focusing on the use of nanocarriers like liposomes, polymeric nanoparticles, and solid lipid nanoparticles. These systems enhanced the efficacy of antimalarial drugs by enabling targeted delivery to malaria-infected cells, overcoming drug resistance, and offering controlled release mechanisms. The review also explored emerging strategies such as combination therapies, personalized nanomedicine, responsive nanoparticles, and vaccine delivery systems. While nanotechnology holds great promise, challenges including safety, scalability, regulatory hurdles, and cost were addressed. Future directions suggest innovations such as smart nanocarriers, personalized treatments, and enhanced diagnostic integration. Methodologically, this review synthesized data from recent preclinical and clinical research to provide a comprehensive analysis of nanotechnology’s role in advancing malaria treatment. Global collaboration and interdisciplinary research will be pivotal in realizing the full potential of nanotechnology in combating malaria. Keywords: Nanotechnology, malaria treatment, drug delivery systems, liposomes, nanoparticles, targeted therapy, drug resistance

Stimuli‐Responsive Nanocarriers as Active Enhancers of Antitumoral Immunotherapy

AbstractIn recent years, the understanding of the role of the immune system in tumor progression and metastasis is paving the way for the development of antitumoral strategies based on the delivery of immunotherapeutic agents. The engineering of stimuli‐responsive nanocarriers able to release their payload in a controlled manner being able to boost potent and sustained immune responses against tumors has provided a powerful tool to eradicate tumors with extreme precision. Paramount advantages to trigger the immune system against tumors are the high selectivity and memory effect of immune response, which allows not only to eradicate primary and metastatic malignancies but also to avoid their relapse. In this review, the recent advances carried out in the development of smart nanocarriers for immunotherapy are presented.

Achieving Endo/Lysosomal Escape Using Smart Nanosystems for Efficient Cellular Delivery.

The delivery of therapeutic agents faces significant hurdles posed by the endo-lysosomal pathway, a bottleneck that hampers clinical effectiveness. This comprehensive review addresses the urgent need to enhance cellular delivery mechanisms to overcome these obstacles. It focuses on the potential of smart nanomaterials, delving into their unique characteristics and mechanisms in detail. Special attention is given to their ability to strategically evade endosomal entrapment, thereby enhancing therapeutic efficacy. The manuscript thoroughly examines assays crucial for understanding endosomal escape and cellular uptake dynamics. By analyzing various assessment methods, we offer nuanced insights into these investigative approaches' multifaceted aspects. We meticulously analyze the use of smart nanocarriers, exploring diverse mechanisms such as pore formation, proton sponge effects, membrane destabilization, photochemical disruption, and the strategic use of endosomal escape agents. Each mechanism's effectiveness and potential application in mitigating endosomal entrapment are scrutinized. This paper provides a critical overview of the current landscape, emphasizing the need for advanced delivery systems to navigate the complexities of cellular uptake. Importantly, it underscores the transformative role of smart nanomaterials in revolutionizing cellular delivery strategies, leading to a paradigm shift towards improved therapeutic outcomes.

Nanoliposomes as nonviral vectors in cancer gene therapy.

Nonviral vectors, such as liposomes, offer potential for targeted gene delivery in cancer therapy. Liposomes, composed of phospholipid vesicles, have demonstrated efficacy as nanocarriers for genetic tools, addressing the limitations of off-targeting and degradation commonly associated with traditional gene therapy approaches. Due to their biocompatibility, stability, and tunable physicochemical properties, they offer potential in overcoming the challenges associated with gene therapy, such as low transfection efficiency and poor stability in biological fluids. Despite these advancements, there remains a gap in understanding the optimal utilization of nanoliposomes for enhanced gene delivery in cancer treatment. This review delves into the present state of nanoliposomes as carriers for genetic tools in cancer therapy, sheds light on their potential to safeguard genetic payloads and facilitate cell internalization alongside the evolution of smart nanocarriers for targeted delivery. The challenges linked to their biocompatibility and the factors that restrict their effectiveness in gene delivery are also discussed along with exploring the potential of nanoliposomes in cancer gene therapy strategies by analyzing recent advancements and offering future directions.

The smart nanocarrier containing zein/starch co-biopolymers enhanced by graphitic carbon nitride; exploring opportunities in brain cancer treatment

In this investigation, we present an innovative pH-responsive nanocomposite designed to address challenges associated with using 5-Fluorouracil (5-FU) in cancer therapy. The nanocomposite containing zein (Z), starch (S), and graphitic carbon nitride (g-C3N4) macromolecules is synthesized by a water-in-oil-in-water (W/O/W) double emulsion technique, serving as a carrier for 5-FU. The S/Z hydrogel matrix's entrapment and loading efficiency are greatly improved by adding g-C3N4 nanosheets, reaching noteworthy values of 45.25 % and 86.5 %, respectively, for drug loading efficiency and entrapment efficiency. Characterization through FTIR and XRD validates the successful loading of 5-FU, elucidating the chemical bonding within the nanocomposite and crystalline characteristics. Structural analysis using FESEM, along with DLS and zeta potential measurements, reveals an average nanocomposite size of 193.48 nm, indicating a controlled structure, and a zeta potential of −42.32 mV, signifying a negatively charged surface. Studies on the in vitro release of drugs reveal that 5-FU is delivered more effectively and sustainably in acidic environments than in physiological circumstances. This highlights the fact that the created nanocarrier is pH-sensitive. Modeling release kinetics involves finding the right mathematical conditions representing underlying physicochemical processes. Employing curve-fitting techniques, predominant release mechanisms are identified, and optimal-fitting kinetic models are determined. The Baker kinetic model performed best at pH 7.4, indicating that the leading cause of the drug release was polymer swelling. In contrast, the Higuchi model was most accurate for drug release at pH 5.4, illuminating the diffusion and dissolution mechanisms involved in diffusion. To be more precise, the mechanism of release at pH 7.4 and 5.4 was anomalous transport (dissolution-controlled), according to the Korsmeyer-Peppas mathematical model. The pH-dependent swelling and degradation behavior of S/Z/g-C3N4@5-FU nanocomposite showed higher swelling and faster degradation in acidic environments compared to neutral conditions. Crucially, outcomes from the MTT test affirm the significant cytotoxicity of the 5-FU-loaded nanocomposite against U-87 MG brain cancer cells, while simultaneously indicating non-toxicity towards L929 fibroblast cells. These cumulative findings underscore the potential of the engineered S/Z/g-C3N4@5-FU as a productive and targeted therapeutic approach for cancer cells.

Dual-trigger release of berberine chloride from the gelatin/perfluorohexane core–shell structure

BackgroundThe development of smart nanocarriers that enable controlled drug release in response to internal and external triggers is an emerging approach for targeted therapy. This study focused on designing pH-sensitive, ultrasound-responsive gelatin/perfluorohexane (PFH) nanodroplets loaded with berberine chloride as a model drug.ResultsThe nanodroplets were prepared using an emulsion technique and optimized by varying process parameters like homogenization rate, polymer concentration, surfactant, drug, and perfluorocarbon content. The optimal formulation yielded nanodroplets with a particle size of 281.7 nm, a drug encapsulation efficiency of 66.8 ± 1.7%, and a passive drug release of 15.4 ± 0.2% within 24 h. Characterization confirmed successful encapsulation and pH-responsive behavior. Ultrasound stimulation significantly enhanced drug release, with 150 kHz being more effective than 1 MHz in triggering acoustic droplet vaporization while minimizing heat generation. After 10 min of radiation, the optimal formulation showed 89.4% cumulative drug release. The nanodroplets displayed stability over 1 month at 4°C.ConclusionsOverall, the dual-triggered nanodroplets demonstrate excellent potential for controlled delivery and targeted release of berberine chloride.Graphical abstract

Evodiamine and its nano-based approaches for enhanced cancer therapy: recent advances and challenges.

Evodiamine is a bioactive alkaloid extracted from the Evodia rutaecarpa plant. It has various pharmacological effects including anti-cancer, anti-bacterial, anti-obesity, anti-neurodegenerative, anti-depressant, and cardiac protective properties. Evodiamine demonstrates potent anti-cancer activity by inhibiting the proliferation of cancer cells in vitro and in vivo. Despite the health-promoting properties of evodiamine, its clinical use is hindered by low water solubility, poor bioavailability, and toxicity. Thus, there is a need to develop alternative drug delivery systems for evodiamine to enhance its solubility, permeability, and stability, as well as to facilitate targeted, prolonged, and controlled drug release. Nanocarriers can increase the therapeutic potential of evodiamine in cancer therapy while reducing adverse side effects. To date, numerous attempts have been made through the development of smart nanocarriers to overcome the drawbacks of evodiamine. This review focuses on the pharmacological applications, anti-cancer mechanisms, and limitations of evodiamine. Various nanocarriers, including lipid-based nanoparticles, polymeric nanoparticles, cyclodextrins, and so forth, have been discussed extensively for evodiamine delivery. Nano-drug delivery systems could increase the solubility, bioavailability, stability, and therapeutic efficacy of evodiamine. This review aims to present a comprehensive and critical evaluation of several nano-formulations of evodiamine for cancer therapy. © 2024 Society of Chemical Industry.

Wireless sequential dual light delivery for programmed PDT in vivo

Using photodynamic therapy (PDT) to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light. Polymeric nanocarriers are widely used for photosensitizer delivery, while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy. Furthermore, the generated short-lived reactive oxygen spieces (ROS) can hardly diffuse out of nanocarriers, resulting in low PDT efficacy. Therefore, a smart nanocarrier system which can be degraded by light, followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy. A light-sensitive polymer nanocarrier encapsulating photosensitizer (RB-M) was synthesized. An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer. Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently. Optimal irradiation time, dose, and RB-M concentration were determined using an agent-based digital simulation method. In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose, which is a clinically significant event that enhances treatment safety.

Ti3C2 (MXene), an advanced carrier system: role in photothermal, photoacoustic, enhanced drugs delivery and biological activity in cancer therapy.

In the realm of healthcare and the advancing field of medical sciences, the development of efficient drug delivery systems become an immense promise to cure several diseases. Despite considerable advancements in drug delivery systems, numerous challenges persist, necessitating further enhancements to optimize patient outcomes. Smart nano-carriers, for instance, 2D sheets nano-carriers are the recently emerging nanosheets that may garner attention for targeted delivery of bioactive compounds, drugs, and genes to kill cancer cells. Within these advancements, Ti3C2TX-MXene, characterized as a two-dimensional transition metal carbide, has surfaced as a prominent intelligent nanocarrier within nanomedicine. Its noteworthy characteristics facilitated it as an ideal nanocarrier for cancer therapy. In recent advancements in drug delivery research, Ti3C2TX-MXene 2D nanocarriers have been designed to release drugs in response to specific stimuli, guided by distinct physicochemical parameters. This review emphasized the multifaceted role of Ti3C2TX-MXene as a potential carrier for delivering poorly hydrophilic drugs to cancer cells, facilitated by various polymer coatings. Furthermore, beyond drug delivery, this smart nanocarrier demonstrates utility in photoacoustic imaging and photothermal therapy, further highlighting its significant role in cellular mechanisms.

A Nanorobotics-Based Approach of Breast Cancer in the Nanotechnology Era.

We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating in nanorobots, have demonstrated ingenious applications in biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem of BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance to classic onco-therapies and real-time monitoring of tumors, nanorobots are designed to perform multiple tasks at a small scale, even at the organelles or molecular level. Over the last few years, most nanorobots have been bioengineered as biomimetic and biocompatible nano(bio)structures, resembling different organisms and cells, such as urchin, spider, octopus, fish, spermatozoon, flagellar bacterium or helicoidal cyanobacterium. In this review, readers will be able to deepen their knowledge of the structure, behavior and role of several types of nanorobots, among other nanomaterials, in BC theranostics. We summarized here the characteristics of many functionalized nanodevices designed to counteract the main neoplastic hallmark features of BC, from sustaining proliferation and evading anti-growth signaling and resisting programmed cell death to inducing angiogenesis, activating invasion and metastasis, preventing genomic instability, avoiding immune destruction and deregulating autophagy. Most of these nanorobots function as targeted and self-propelled smart nano-carriers or nano-drug delivery systems (nano-DDSs), enhancing the efficiency and safety of chemo-, radio- or photodynamic therapy, or the current imagistic techniques used in BC diagnosis. Most of these nanorobots have been tested in vitro, using various BC cell lines, as well as in vivo, mainly based on mice models. We are still waiting for nanorobots that are low-cost, as well as for a wider transition of these favorable effects from laboratory to clinical practice.

NanoBiofertilizer and its Application in Sustainable Agriculture, Crop Specific Nutrients Delivery and Environmental Sustainability: A Review

Probiotic bacteria are increasingly in demand in the food and feed industries. A growing population and finite resources require efficient ways to maximize yields. Probiotic bacteria are gaining popularity in the food and feed industries due to their unique combination of benefits and values, which include consumer health interests, sustainability values, food innovation, and potential business opportunities. The use of conventional fertilizers can increase crop production but can also cause runoff and toxicity issues. A nanobiofertilizer offers improved crop nutrition and reduces application rates. Slow-release properties minimize environmental losses while nanoscale particle size enhances nutrient absorption. If nanobiofertilizers are closely regulated, they can boost yields without destroying the soil and aquatic ecosystems. In recent years, nanobiofertilizers have received considerable attention. Plant extracts and microbes are used in green synthesis to produce eco-friendly nanoparticles. Crop-specific nutrient release can be tailored using modified nanoparticle surfaces. Controlled nutrient delivery is achieved by smart nanocarrier systems that adapt to changing soil moisture, pH, and microbial activity. Combined applications of plant growth-promoting rhizobacteria have been reported that they can enhance crop growth in synergy. This review presents an overview of the most recent studies on nanobiofertilizers, as well as the issues connected with their environmental implications, safety, and regulation, presenting a roadmap for the responsible use of nanobiofertilizers, which aims to enhance food security while protecting the environment for future generations.

A silica nanobean carrier utilizing lysosomal and mitochondrial autophagy to kill ovarian cancer cell

The development of responsive and smart drug nanocarriers that defeat the tumor microenvironment that resists cancer therapy has attracted considerable attention in recent decades. Upgrades are sought to effectively increase the therapeutic efficacy of chemotherapy drugs and reduce damage to normal tissues. In this study, a new type of silica nano-particle carrier, dual-functionalized mesoporous silica nanobeans (DF-MSNB), is used to encapsulate the drug, doxorubicin (DOX), to form the DOX@DF-MSNB complex. The complex simultaneously releases drugs and tracks drug uptake by cells after the environmentally triggered release of the encapsulated drug and fluorophore. Upon sensing the high GSH level and low pH in the tumor microenvironment, the disulfide bond breaks in the linker between the drug and the carrier. An attached fluorescent group is activated, and the DOX drug is released from the carrier. Our results show that DOX@DF-MSNB co-localizes with mitochondria and lysosomes in A2780 cells, enabling DOX to subvert the cells’ mitochondrial function and activate macrophage and mitochondrial autophagy. The application of a mitochondrial autophagy inhibitor confirms that DOX@DF-MSNB inhibits tumor development by activating mitochondrial autophagy.

Preparation and Optimization of MiR-375 Nano-Vector Using Two Novel Chitosan-Coated Nano-Structured Lipid Carriers as Gene Therapy for Hepatocellular Carcinoma.

Currently, there is still a lack of effective carriers with minimal side effects to deliver therapeutic miRNA. Thus, it is crucial to optimize novel drug delivery systems. MiR-375 has proven superior therapeutic potency in Hepatocellular carcinoma (HCC). The purpose of this study was to fabricate 2 novel and smart nano-carriers for the transportation efficiency of miR-375 in HCC cells and enhance its anti-tumor effects. We established the miR-375 construct through the pEGP- miR expression vector. Two nano-carriers of solid/liquid lipids and chitosan (CS) were strategically selected, prepared by high-speed homogenization, and optimized by varying nano-formulation factors. Thus, the two best nano-formulations were designated as F1 (0.5% CS) and F2 (1.5% CS) and were evaluated for miR-375 conjugation efficiency by gel electrophoresis and nanodrop assessment. Then, physio-chemical characteristics and stability tests for the miR-375 nano-plexes were all studied. Next, its efficiencies as replacement therapy in HepG2 cells have been assessed by fluorescence microscopy, flow cytometry, and cytotoxicity assay. The obtained data showed that two cationic nanostructured solid/liquid lipid carriers (NSLCs); F1 and F2 typically had the best physio-chemical parameters and long-term stability. Moreover, both F1 and F2 could form nano-plexes with the anionic miR-375 construct at weight ratios 250/1 and 50/1 via electrostatic interactions. In addition, these nano-plexes exhibited physical stability after three months and protected miR-375 from degradation in the presence of 50% fetal bovine serum (FBS). Furthermore, both nano-plexes could simultaneously deliver miR-375 into HepG2 cells and they ensure miR re-expression even in the presence of 50% FBS compared to free miR-375 (p-value < 0.001). Moreover, both F1 and F2 alone significantly exhibited minimal cytotoxicity in treated cells. In contrast, the nano-plexes significantly inhibited cell growth compared to free miR-375 or doxorubicin (DOX), respectively. More importantly, F2/miR-375 nano-plex exhibited more anti-proliferative activity in treated cells although its IC50 value was 55 times lower than DOX (p-value < 0.001). Collectively, our findings clearly emphasized the multifunctionality of the two CS-coated NSLCs in terms of their enhanced biocompatibility, biostability, conjugation, and transfection efficiency of therapeutic miR-375. Therefore, the NSLCs/miR-375 nano-plexes could serve as a novel and promising therapeutic strategy for HCC.

Smart Nanocarriers for the Treatment of Retinal Diseases.

Retinal diseases, such as age-related macular degeneration, diabetic retinopathy, and retinoblastoma, stand as the leading causes of irreversible vision impairment and blindness worldwide. Effectively administering drugs for retinal diseases poses a formidable challenge due to the presence of complex ocular barriers and elimination mechanisms. Over time, various approaches have been developed to fabricate drug delivery systems for improving retinal therapy including virus vectors, lipid nanoparticles, and polymers. However, conventional nanocarriers encounter issues related to the controllability, efficiency, and safety in the retina. Therefore, the development of smart nanocarriers for effective or more invasive long-term treatment remains a desirable goal. Recently, approaches have surfaced for the intelligent design of nanocarriers, leveraging specific responses to external or internal triggers and enabling multiple functions for retinal therapy such as topical administration, prolonged drug release, and site-specific drug delivery. This Review provides an overview of prevalent retinal pathologies and related pharmacotherapies to enhance the understanding of retinal diseases. It also surveys recent developments and strategies employed in the intelligent design of nanocarriers for retinal disease. Finally, the challenges of smart nanocarriers in potential clinical retinal therapeutic applications are discussed to inspire the next generation of smart nanocarriers.

Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management.

As an indispensable part of the human sensory system, visual acuity may be impaired and even develop into irreversible blindness due to various ocular pathologies. Among ocular diseases, fundus neovascularization diseases (FNDs) are prominent etiologies of visual impairment worldwide. Intravitreal injection of anti-vascular endothelial growth factor drugs remains the primary therapy but is hurdled by common complications and incomplete potency. To renovate the current therapeutic modalities, nanomedicine emerged as the times required, which is endowed with advanced capabilities, able to fulfill the effective ocular fundus drug delivery and achieve precise drug release control, thus further improving the therapeutic effect. This review provides a comprehensive summary of advances in nanomedicine for FND management from state-of-the-art studies. First, the current therapeutic modalities for FNDs are thoroughly introduced, focusing on the key challenges of ocular fundus drug delivery. Second, nanocarriers are comprehensively reviewed for ocular posterior drug delivery based on the nanostructures: polymer-based nanocarriers, lipid-based nanocarriers, and inorganic nanoparticles. Thirdly, the characteristics of the fundus microenvironment, their pathological changes during FNDs, and corresponding strategies for constructing smart nanocarriers are elaborated. Furthermore, the challenges and prospects of nanomedicine for FND management are thoroughly discussed.