Paradigm For Drug Delivery Research Articles

Starch-based "smart" nanomicelles: Potential delivery systems for doxorubicin.

Vesicular nanosystems are a cornerstone to the contemporary drug delivery paradigm owing to their ability to encapsulate a variety of drug molecules, which improves the overall pharmacokinetics and bioavailability of the cargo drug. These systems have proven potential in the delivery of hydrophobic chemotherapeutic "Doxorubicin" (DOX), which faces frequent challenge relating to its nonspecific interactions, dose-limiting toxicity (myelosuppression being the most common manifestation), and short half-life (distribution half-life of 5 min, terminal half-life of 20-48 h), which limit its overall clinical effectiveness. "Smart" nanomicelles with stimuli-responsive linkages take advantage of tumor microenvironment for deploying the cargo drug at the target site, which prevents nonspecific distribution and, hence, low toxicity. Similarly, those with stealth properties evade protein response, which triggers the immunogenic response. The nanomicelles co-loaded with magnetic nanoparticles provide additional utility such as contrast enhancement agents in theranostics. Overall, the starch-based nanomicelles prove to be an excellent delivery system for overcoming the limitations associated with the conventional DOX delivery regime.

Precision Nanomedicine with Bio-Inspired Nanosystems: Recent Trends and Challenges in Mesenchymal Stem Cells Membrane-Coated Bioengineered Nanocarriers in Targeted Nanotherapeutics.

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and restrictions associated with naïve or free forms of therapeutic compounds and circumvent various physicochemical and immunological barriers including but not limited to systemic barriers, microenvironmental roadblocks, and other cellular or subcellular hinderances-which are quite heterogeneous throughout the diseases and patient cohorts. These limitations in drug delivery have been overcome through mesenchymal cells membrane-based precision therapeutics, where these interventions have led to the significant enhancements in therapeutic efficacies. However, the formulation and development of nanocarriers still focuses on optimization of drug delivery paradigms with a one-size-fits-all resolutions. As mesenchymal stem cell membrane-based nanocarriers have been engineered in highly diversified fashions, these are being optimized for delivering the drug payloads in more and better personalized modes, entering the arena of precision as well as personalized nanomedicine. In this Review, we have included some of the advanced nanocarriers which have been designed and been utilized in both the non-personalized as well as precision applicability which can be employed for the improvements in precision nanotherapeutics. In the present report, authors have focused on various other aspects of the advancements in stem cells membrane-based nanoparticle conceptions which can surmount several roadblocks and barriers in drug delivery and nanomedicine. It has been suggested that well-informed designing of these nanocarriers will lead to appreciable improvements in the therapeutic efficacy in therapeutic payload delivery applications. These approaches will also enable the tailored and customized designs of MSC-based nanocarriers for personalized therapeutic applications, and finally amending the patient outcomes.

A Data Mining Study of Zinc Oxide Nanostructures Utilization in Drug Delivery Nanosystems

AbstractThe present investigation offers a thorough bibliometric exploration spotlighting the pivotal utilization of zinc oxide nanostructures, encompassing both zero‐dimensional (0D) nanoparticles and one‐dimensional (1D) nanostructures, within the realm of nanotechnology‐driven drug delivery systems. This analysis particularly illuminates the distinctive potential of these nanostructures in the cancer therapy context, not merely as carriers and deliverers of pharmaceutical agents, but as entities capable of selectively inducing apoptosis in cancer cells through the orchestrated generation of reactive oxygen species (ROS). Recent research endeavors notably underscore the application prospects of ZnO nanostructures in domains like DNA cleavage, bioimaging, and agricultural defense mechanisms. Moreover, the study elucidates the pronounced enhancement in solubility and biocompatibility that these nanostructures bring about when harmoniously integrated into polymeric nanocomposites. Concomitantly, the involvement of polymers in this symbiotic system is unveiled, wherein they play a multifaceted role in dictating release selectivity, thereby facilitating targeted and efficacious interactions with tissues. Functionally engineered polymeric nanocomposites emerge as promising candidates for targeted delivery modalities in cancer treatment, demonstrating an affinity for specific cell receptors and exhibiting enhanced cellular uptake within the size range of 100–200 nm. The study unearths robust associations among pivotal research terminologies through an exhaustive analysis of Link Strength Between Items (LSBI), culminating in the presentation of a cogent map delineating the evolving trends and forthcoming trajectories in this dynamic domain. In summation, this all‐encompassing bibliometric inquiry serves as a poignant testament to the prodigious potential of zinc oxide nanostructures in the realm of forthcoming nanotechnology‐driven drug delivery paradigms.

Utilization of nanotechnology and experimental design in the development and optimization of a posaconazole‒calendula oil nanoemulgel for the treatment of mouth disorders.

Introduction: Essential oil‒based nanoemulsions (NEs) are the subjects of extensive investigation due to their potential to address a variety of oral health issues. NEs are delivery systems that improve lipid medicine solubility and distribution to intended sites. The goal of the current study was to create and enhance a self-nanoemulsifying drug delivery paradigm based on calendula oil (CO) and decorated with chitosan (CS) that could deliver posaconazole (PSZ) for the treatment of gingivitis. Method: Employing a response-surface Box‒Behnken design, PSZ-CO-CS NEs were created with varying amounts of PSZ (10, 15, and 20mg), percentages of CO (6%, 12%, and 18%), and percentages of CS (0.5%, 1.5%, and 2.5%). Results and conclusion: The optimized formulation resulted in a 22-mm bacterial growth suppression zone, 25-mm fungal growth inhibition zone, droplet sizes of 110nm, and a viscosity of 750 centipoise (cP). Using the appropriate design, the ideal formulation was produced; it contained 20mg of PSZ, 18% of CO, and 1.35% of CS. Furthermore, the optimal formulation had a more controlled drug release, larger inhibition zones of bacterial and fungal growth, and desirable rheologic properties. Additionally, the optimized formulation substantially lowered the ulcer index in rats when tested against other formulations. Thus, this investigation showed that PSZ-CO-CS NEs could provide efficient protection against microbially induced gingivitis.

Early Stage Preclinical Formulation Strategies to Alter the Pharmacokinetic Profile of Two Small Molecule Therapeutics.

Early stage chemical development presents numerous challenges, and achieving a functional balance is a major hurdle, with many early compounds not meeting the clinical requirements for advancement benchmarks due to issues like poor oral bioavailability. There is a need to develop strategies for achieving the desired systemic concentration for these compounds. This will enable further evaluation of the biological response upon a compound-target interaction, providing deeper insight into the postulated biological pathways. Our study elucidates alternative drug delivery paradigms by comparing formulation strategies across oral (PO), intraperitoneal (IP), subcutaneous (SC), and intravenous (IV) routes. While each modality boasts its own set of merits and constraints, it is the drug's formulation that crucially influences its pharmacokinetic (PK) trajectory and the maintenance of its therapeutic levels. Our examination of model compounds G7883 and G6893 highlighted their distinct physio-chemical attributes. By harnessing varied formulation methods, we sought to fine-tune their PK profiles. PK studies showcased G7883's extended half-life using an SC oil formulation, resulting in a 4.5-fold and 2.5-fold enhancement compared with the IP and PO routes, respectively. In contrast, with G6893, we achieved a prolonged systemic coverage time above the desired target concentration through a different approach using an IV infusion pump. These outcomes underscore the need for tailored formulation strategies, which are dictated by the compound's innate properties, to reach the optimal in vivo systemic concentrations. Prioritizing formulation and delivery optimization early on is pivotal for effective systemic uptake, thereby facilitating a deeper understanding of biological pathways and expediting the overall clinical drug development timeline.

Advancing Drug Delivery Paradigms: Polyvinyl Pyrolidone (PVP)-Based Amorphous Solid Dispersion for Enhanced Physicochemical Properties and Therapeutic Efficacy.

The current challenge in drug development lies in addressing the physicochemical issues that lead to low drug effectiveness. Solubility, a crucial physicochemical parameter, greatly influences various biopharmaceutical aspects of a drug, including dissolution rate, absorption, and bioavailability. Amorphous solid dispersion (ASD) has emerged as a widely explored approach to enhance drug solubility. The objective of this review is to discuss and summarize the development of polyvinylpyrrolidone (PVP)-based amorphous solid dispersion in improving the physicochemical properties of drugs, with a focus on the use of PVP as a novel approach. This review was conducted by examining relevant journals obtained from databases such as Scopus, PubMed, and Google Scholar, since 2018. The inclusion and exclusion criteria were applied to select suitable articles. This study demonstrated the versatility and efficacy of PVP in enhancing the solubility and bioavailability of poorly soluble drugs. Diverse preparation methods, including solvent evaporation, melt quenching, electrospinning, coprecipitation, and ball milling are discussed for the production of ASDs with tailored characteristics. PVP-based ASDs could offer significant advantages in the formulation strategies, stability, and performance of poorly soluble drugs to enhance their overall bioavailability. The diverse methodologies and findings presented in this review will pave the way for further advancements in the development of effective and tailored amorphous solid dispersions.

Nanomedicine Redefining Cancer Therapeutics: The Evolution of Precision Drug Delivery Systems

With the advent of nanomedicines including drug delivery carriers such as nanoparticles, liposomes, nanoemulsions, and micelles, there has been a paradigm shift in the sphere of cancer treatment. These nano-biosystems have been the focus of scientific research in recent years due to their biocompatibility, low toxicity, higher retention time, bioavailability and higher targeted efficiency as compared to conventional therapeutics such as chemotherapy, radiotherapy and immunotherapy. These conventional therapies not only target cancerous cells but negatively affect neighboring health cells as well comprising the individuals’ immune health. Therefore, nanomaterials have been considered the foremost strategy to combat different types of cancer. To facilitate delivery and provide a “stealthy character” to nanomaterials, biomimetic (cell-derived) surface coatings and encapsulations have been developed. Red blood cell mimetic nanoparticles have been designed to successfully inhibit the growth and metastasis of breast carcinoma. Similarly, HeLa cell membrane-derived vesicles of GdTPP/ZnTPP porphyrin nanocomposites have been utilized for photodynamic therapy (PDT) for cervical carcinoma [1]. In addition, ferritin-based and vault-protein nanocarriers have been designed using recombinant engineering techniques to overcome the barriers of multidrug resistance and in-vivo drug delivery reducing immune response and increasing the effectiveness of anticancerous drugs. These functionalized nanocarriers have been reported against glioma, melanoma, hepatocarcinoma, adenocarcinoma and lung cancer [2]. A considerable number of nanomedicines have passed clinical trials and been approved for commercial use by various regulatory organizations. The most recent being the NanoTherm, an EMA-approved nanomedicine for glioblastoma, prostate cancer, and pancreatic cancer. It is a superparamagnetic iron oxide nanoparticle covered with aminosilane [3]. With precision, efficacy, and promise for both patients and clinicians, nanomedicine is a sign of a new era in cancer therapies. Harnessing the potential of nanomedicine demands teamwork, innovation, and transforming ground-breaking research into game-changing clinical applications as we navigate this rapidly changing landscape. With the goal of bringing targeted, personalized cancer treatments closer to reality, this editorial seeks to highlight the unmatched potential of nanomedicine in transforming drug delivery paradigms. 

3D printing in biomedicine: advancing personalized care through additive manufacturing

The integration of three-dimensional (3D) printing techniques into the domains of biomedical research and personalized medicine highlights the evolving paradigm shifts within contemporary healthcare. This technological advancement signifies potential breakthroughs in patient-specific therapeutic interventions and innovations. This systematic review offers a critical assessment of the existing literature, elucidating the present status, inherent challenges, and prospective avenues of 3D printing in augmenting biomedical applications and formulating tailored medical strategies. Based on an exhaustive literature analysis comprising empirical studies, case studies, and extensive reviews from the past decade, pivotal sectors including tissue engineering, prosthetic development, drug delivery systems, and customized medical apparatuses are delineated. The advent of 3D printing provides precision in the fabrication of patient-centric implants, bio-structures, and devices, thereby mitigating associated risks. Concurrently, it facilitates the ideation of individualized drug delivery paradigms to optimize therapeutic outcomes. Notwithstanding these advancements, issues concerning material biocompatibility, regulatory compliance, and the economic implications of avant-garde printing techniques persist. To fully harness the transformative potential of 3D printing in healthcare, collaborative endeavors amongst academicians, clinicians, industrial entities, and regulatory bodies are paramount. With continued research and innovation, 3D printing is poised to redefine the trajectories of biomedical science and patient-centric care. The paper aims to justify the research objective of whether to what extent the integration of 3D printing technology in biomedicine enhances patient-specific treatment and contributes to improved healthcare outcomes.

Nanomaterials as drug delivery agents for overcoming the blood-brain barrier: A comprehensive review.

The blood-brain barrier (BBB), a critical interface of specialized endothelial cells, plays a pivotal role in regulating molecular and ion transport between the central nervous system (CNS) and systemic circulation. This review aims to delve into the intricate architecture and functions of the BBB while addressing challenges associated with delivering therapeutics to the brain. Historical milestones and contemporary insights underscore the BBB's significance in protecting the CNS. Innovative approaches for enhanced drug transport include intranasal delivery exploiting olfactory and trigeminal pathways, as well as techniques like temporary BBB opening through chemicals, receptors, or focused ultrasound. These avenues hold the potential to reshape conventional drug delivery paradigms and address the limitations posed by the BBB's selectivity. This review underscores the vital role of the BBB in maintaining CNS health and emphasizes the importance of effective drug delivery through this barrier. Nanoparticles emerge as promising candidates to overcome BBB limitations and potentially revolutionize the treatment of CNS disorders. As research progresses, the application of nanomaterials shows immense potential for advancing neurological therapeutics, albeit with careful consideration of safety aspects.

Solid Lipid Nanoparticles: Drug Delivery Systems for Enhancing the Bioavailability of Antihypertensives

The pharmaceutical industry focuses the SLNs as promising drug deliverance methods for improving bioavailability. SLNs are a swiftly budding field of nanotechnology amid plentiful budding applications in medicine and research. Lipid-based nanoparticles possess unique properties due to their small size, allowing novel therapeutics to be developed. The encapsulation of drugs within nano-carriers presents a new paradigm in drug delivery, enabling enhanced targeting at secondary and tertiary levels. Consequently, SLNs have garnered significant attention from researchers for their site-specific drug delivery. This review enlightens on the responsibilities of SLN for improving the pharmacokinetics of poorly soluble antihypertensive drugs. Profound investigations confirmed SLNs have latent to transfigure antihypertensives through enhanced oral delivery.

Cabazitaxel prodrug nanoassemblies with branched chain modifications: Narrowing the gap between efficacy and safety

The clinical application of cabazitaxel (CTX) is restricted by severe dose-related toxicity, failing to considering therapeutic efficacy and safety together. Self-assembled prodrugs promote new drug delivery paradigms as they can self-deliver and self-formulate. However, the current studies mainly focused on the use of straight chains to construct self-assembled prodrugs, and the role of branched chains in prodrug nanoassemblies remains to be clarified. In this study, we systematically explored the structure–function relationship of prodrug nanoassemblies using four CTX prodrugs that contained branched chain aliphatic alcohols (BAs) with different alkyl lengths. Overall, CTX-SS-BA20 NPs with the proper alkyl length exhibited significant improvements in both antitumor efficacy and biosafety. Furthermore, compared with straight chain (SC) modified prodrug nanoassemblies (CTX-SS-SC20 NPs), CTX-SS-BA20 NPs still hold great therapeutic promise due to its good biosafety. These findings illustrated the significance of BAs as modified chains in designing prodrug nanoassemblies for narrowing the efficacy-to-safety gap of cancer therapy.

Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy.

The paradigm of drug delivery via particulate formulations is one of the leading ideas that enable overcoming limitations of traditional chemotherapeutic agents. The trend toward more complex multifunctional drug carriers is well-traced in the literature. Nowadays, the prospectiveness of stimuli-responsive systems capable of controlled cargo release in the lesion nidus is widely accepted. Both endogenous and exogenous stimuli are employed for this purpose; however, endogenous pH is the most common trigger. Unfortunately, scientists encounter multiple challenges on the way to the implementation of this idea related to the vehicles' accumulation in off-target tissues, their immunogenicity, the complexity of drug delivery to intracellular targets, and finally, the difficulties in the fabrication of carriers matching all imposed requirements. Here, we discuss fundamental strategies for pH-responsive drug delivery, as well as limitations related to such carriers' application, and reveal the main problems, weaknesses, and reasons for poor clinical results. Moreover, we attempted to formulate the profiles of an "ideal" drug carrier in the frame of different strategies drawing on the example of metal-comprising materials and considered recently published studies through the lens of these profiles. We believe that this approach will facilitate the formulation of the main challenges facing researchers and the identification of the most promising trends in technology development.

Hybrid Biomimetic Nanovesicles to Drive High Lung Biodistribution and Prevent Cytokine Storm for ARDS Treatment.

Acute respiratory distress syndrome (ARDS) has been a life threat for patients in ICUs. Vast efforts have been devoted, while no medication has proved viable, which may be ascribed to inadequate drug delivery to damaged tissues and insufficient control of lung inflammation. Given the anti-inflammatory role of M2-type macrophages, M2 macrophage-derived nanovesicles and lung-targeting liposomes are cofused to fabricate hybrid liposomes-nanovesicles (LNVs). Benefiting from the incorporated lung-homing moiety, LNVs demonstrate high pulmonary accumulation with a lung/liver ratio of 14.9, which is approximately 53.3-fold of free nanovesicles. Thus, M2 macrophage-derived nanovesicles can be delivered to lung tissues for executing immunoregulatory functions. LNVs display phagocytosis by the infiltrated neutrophils and macrophages, exhibiting sustained release of preloaded IKK-2 inhibitor (TPCA-1). The integrated nanosystems demonstrate multidimensional suppression of the overwhelming inflammation, such as decreasing infiltration of inflammatory cells, achieving restraint on cytokine storms and alleviating oxidative stress. Therefore, the improved therapeutic outcome in ARDS mice is obtained. Altogether, the hybrid nanoplatform provides a versatile drug delivery paradigm for integrating biological nanovesicles and therapeutic molecules by cofusion of nanovesicles with liposomes, improving lung biodistribution and accomplishing a boosted anti-inflammatory response for ARDS therapy.

Promoting Tumor Accumulation of Anticancer Drugs by Hierarchical Carrying of Exogenous and Endogenous Vehicles

Promoting tumor accumulation of active pharmaceutical ingredients is crucial for targeted anticancer therapy. However, this issue has not yet been addressed because of the fast clearance or premature degradation, slow drug release kinetics, and nonspecific biodistribution of the reported formulations. Herein, a new drug delivery paradigm is proposed based on supramolecular hierarchical recognition to achieve high tumor accumulation of anticancer drugs by overcoming these three challenges. The prepared supramolecular ternary formulation of paclitaxel (PTX) contains two steps of molecular recognition: exogenous recognition of PTX by an artificial macrocyclic carrier, sulfonated azocalix[5]arene (SAC5A) in vitro, and endogenous recognition of PTX@SAC5A by intrinsic serum albumin in vivo. The ternary PTX@SAC5A⊂albumin concurrently accomplishes prolonged blood circulation, rapid drug release, and dual passive and hypoxia‐responsive targeting. As a result, the PTX@SAC5A⊂albumin formulation exhibits more efficient tumor accumulation than free PTX and albumin‐based, solvent‐based, liposome‐based, and sulfobutyl ether‐β‐cyclodextrin‐based PTX formulations, thereby contributing to better therapeutic efficacy. The current strategy paves the way for promoting the tumor accumulation of drugs, showing the advantages of simplicity, universality, and reproducibility.

Promising Strategies for Transdermal Delivery of Arthritis Drugs: Microneedle Systems.

Arthritis is a general term for various types of inflammatory joint diseases. The most common clinical conditions are mainly represented by rheumatoid arthritis and osteoarthritis, which affect more than 4% of people worldwide and seriously limit their mobility. Arthritis medication generally requires long-term application, while conventional administrations by oral delivery or injections may cause gastrointestinal side effects and are inconvenient for patients during long-term application. Emerging microneedle (MN) technology in recent years has created new avenues of transdermal delivery for arthritis drugs due to its advantages of painless skin perforation and efficient local delivery. This review summarizes various types of arthritis and current therapeutic agents. The current development of MNs in the delivery of arthritis drugs is highlighted, demonstrating their capabilities in achieving different drug release profiles through different self-enhancement methods or the incorporation of nanocarriers. Furthermore, the challenges of translating MNs from laboratory studies to the clinical practice and the marketplace are discussed. This promising technology provides a new approach to the current drug delivery paradigm in treating arthritis in transdermal delivery.

A SHORT-TERM REVIEW ON SOLID LIPID NANOPARTICLES

In recent years, Solid lipid nanoparticles (SLNs) have been given a lot of attention as a potential drug distribution alternative to existing colloidal dispersion technologies. The use of SLNs as a pharmaceutical carrier has gotten a lot of focus in recent years. Nanostructure lipid carriers and SLNs are non-toxic since they are biodegradable. SLNs have various distinct properties in terms of therapeutic uses. SLNs are lipid-based nanocarriers with sizes ranging between 10 to 1000 nanometers. Decomposition of the drug can be protected by the drug entrapped in a lipid, physical stability; controlled drug release and remarkable acceptability are all benefits of SLNs over traditional drug carriers. The capacity to incorporate pharmaceuticals into nanocarriers opens up a new paradigm in drug delivery that could hold enormous promise in terms of improving bioavailability while also allowing for controlled and site-specific drug delivery. This article covers the manufacture and characterization of SLNs, as well as the administration and medicinal uses.

Ultrasound-Mediated Drug Delivery: Sonoporation Mechanisms, Biophysics, and Critical Factors.

Sonoporation, or the use of ultrasound in the presence of cavitation nuclei to induce plasma membrane perforation, is well considered as an emerging physical approach to facilitate the delivery of drugs and genes to living cells. Nevertheless, this emerging drug delivery paradigm has not yet reached widespread clinical use, because the efficiency of sonoporation is often deemed to be mediocre due to the lack of detailed understanding of the pertinent scientific mechanisms. Here, we summarize the current observational evidence available on the notion of sonoporation, and we discuss the prevailing understanding of the physical and biological processes related to sonoporation. To facilitate systematic understanding, we also present how the extent of sonoporation is dependent on a multitude of factors related to acoustic excitation parameters (ultrasound frequency, pressure, cavitation dose, exposure time), microbubble parameters (size, concentration, bubble-to-cell distance, shell composition), and cellular properties (cell type, cell cycle, biochemical contents). By adopting a science-backed approach to the realization of sonoporation, ultrasound-mediated drug delivery can be more controllably achieved to viably enhance drug uptake into living cells with high sonoporation efficiency. This drug delivery approach, when coupled with concurrent advances in ultrasound imaging, has potential to become an effective therapeutic paradigm.

On-Demand Drug Release from Click-Refillable Drug Depots.

Stimuli-responsive, on-demand release of drugs from drug-eluting depots could transform the treatment of many local diseases, providing intricate control over local dosing. However, conventional on-demand drug release approaches rely on locally implanted drug depots, which become spent over time and cannot be refilled or reused without invasive procedures. New strategies to noninvasively refill drug-eluting depots followed by on-demand release could transform clinical therapy. Here we report an on-demand drug delivery paradigm that combines bioorthogonal click chemistry to locally enrich protodrugs at a prelabeled site and light-triggered drug release at the target tissue. This approach begins with introduction of the targetable depot through local injection of chemically reactive azide groups that anchor to the extracellular matrix. The anchored azide groups then capture blood-circulating protodrugs through bioorthogonal click chemistry. After local capture and retention, active drugs can be released through external light irradiation. In this report, a photoresponsive protodrug was constructed consisting of the chemotherapeutic doxorubicin (Dox), conjugated to dibenzocyclooctyne (DBCO) through a photocleavable ortho-nitrobenzyl linker. The protodrug exhibited excellent on-demand light-triggered Dox release properties and light-mediated in vitro cytotoxicity in U87 glioblastoma cell lines. Furthermore, in a live animal setting, azide depots formed in mice through intradermal injection of activated azide-NHS esters. After i.v. administration, the protodrug was captured by the azide depots with intricate local specificity, which could be increased with multiple refills. Finally, doxorubicin could be released from the depot upon light irradiation. Multiple rounds of depot refilling and light-mediated release of active drug were accomplished, indicating that this system has the potential for multiple rounds of treatment. Taken together, these in vitro and in vivo proof of concept studies establish a novel method for in vivo targeting and on-demand delivery of cytotoxic drugs at target tissues.

How can smart dressings change the future of wound care?

How can smart dressings change the future of wound care?

Deeply Infiltrating iRGD-Graphene Oxide for the Intensive Treatment of Metastatic Tumors through PTT-Mediated Chemosensitization and Strengthened Integrin Targeting-Based Antimigration.

A limited infiltration and the subsequent low effective drug concentration result in poor chemotherapeutic outcomes against tumors, and even further promote tumor resistance and metastatic. Herein, iRGD-modified graphene oxide (GO) nanosheets (IPHG) are developed for the intensive treatment of metastatic tumors using focus-specific penetrated delivery together with photothermal therapy-mediated chemosensitization and photothermal therapy-strengthened integrin targeting-based antimigration. In vitro and in vivo data verified the mechanism of the tumor-selective infiltration of IPHG is based on a rigid 2D structure-associated advantage regarding hemodynamics and endothelial contact, followed by iRGD-endowed transendothelial and intratumoral transport. Once IPHG-DOX-penetrated 4T1 tumors are exposed to near-infrared irradiation, hyperthermia stress and photothermal therapy-elevated effective drug concentrations result in chemosensitization and prominent tumor suppression. Meanwhile, the specific binding of iRGD to integrins and photothermal therapy leads to the synergistic perturbation of cytoskeleton remodeling and subsequent impairment of cell motility and metastasis. The tailored design of IPHG validates a promising paradigm for drug delivery to combat tumor resistance and metastasis resulting from poor target access for single chemotherapy.