Gradual Drug Release Research Articles

Enhanced Intratumoral Delivery of Immunomodulator Monophosphoryl Lipid A through Hyperbranched Polyglycerol–Coated Biodegradable Nanoparticles

Immunomodulatory agents (IMA) have significant potential to enhance cancer treatment but have demonstrated limited efficacy beyond the preclinical setting due to poor pharmacokinetics and toxicity associated with systemic administration. On the other hand, when locally delivered, IMAs require repeated administration to optimize immune stimulation. To overcome these challenges, we encapsulated the toll-like receptor (TLR)4 agonist monophosphoryl lipid A (MPLA) within hyperbranched polyglycerol (HPG)-coated biodegradable nanoparticles (NP) engineered for gradual drug release from the nanoparticle core, resulting in a more persistent stimulation of anti-tumor immune responses while minimizing systemic side effects. In a model of malignant melanoma, we demonstrate that HPG-NP encapsulation significantly improves the antitumor efficacy of MPLA by enhancing its ability to remodel the tumor microenvironment (TME). Compared to free MPLA, HPG-NP-MPLA significantly increased the natural killer cell and cytotoxic T cell mediated antitumor immune response and tuned the tumor draining lymph nodes towards a T helper (Th)1 response. Furthermore, when combined with local delivery of a chemotherapeutic agent, HPG-NP-MPLA induces the conversion of an immunosuppressive TME to immunogenic TME and significantly improves survival.

Controlled curcumin delivery via carboxymethyl starch‐modified gamma alumina nanoparticles in a polyethylene glycol‐based hydrogel

AbstractOne of the most prevalent cancers affecting women globally is breast cancer. Consequently, the development of cost‐effective and low‐risk treatment options remains a critical pursuit. This study describes the synthesis via water‐in‐oil‐in‐water (W/O/W) of a pH‐responsive nanocarrier for curcumin delivery, a promising anticancer drug. The nanocarrier comprises carboxymethyl starch (CMS), polyethylene glycol (PEG), and gamma alumina (γ‐Al2O3) nanoparticles. The molecular interactions between the nanocomposite components, its crystalline structure, surface morphology, size distribution, and surface charge were assessed via Fourier‐transformed infrared (FTIR) spectroscopy, field emission‐scanning electron microscopy (FE‐SEM), x‐ray diffraction (XRD), dynamic light scattering (DLS) and zeta potential, respectively. The nanocarrier showed a size ranging from 150 to 280 nm, zeta potential of +35.4 mV, drug loading of 47% and an encapsulation efficiency of 87%, which are among the maximum values reported to date for curcumin nanocarriers. A gradual drug release was observed, with 51% and 90% released after 72 h at pH 7.4 and 5.4, respectively, which corroborates the pH‐sensitivity of the nanocarrier. The cytotoxic effects of the curcumin‐loaded nanocomposite on MCF‐7 breast cancer cells and normal cells were investigated using methylthiazolyldiphenyl‐tetrazolium bromide (MTT) assay and flow cytometry. The results demonstrated that loading curcumin onto the hydrogel significantly enhances its penetration into MCF‐7 cells. Overall, this novel nanocomposite offers a promising approach for curcumin delivery in breast cancer treatment.

Near-Infrared-Responsive Nanofiber Hydrogel with Gradual Drug Release Properties for Wound Healing

Near-Infrared-Responsive Nanofiber Hydrogel with Gradual Drug Release Properties for Wound Healing

Antitumoral-Embedded Biopolymeric Spheres for Implantable Devices.

The bioactive surface modification of implantable devices paves the way towards the personalized healthcare practice by providing a versatile and tunable approach that increase the patient outcome, facilitate the medical procedure, and reduce the indirect or secondary effects. The purpose of our study was to assess the performance of composite coatings based on biopolymeric spheres of poly(lactide-co-glycolide) embedded with hydroxyapatite (HA) and methotrexate (MTX). Bio-simulated tests performed for up to one week evidenced the gradual release of the antitumor drug and the biomineralization potential of PLGA/HA-MTX sphere coatings. The composite materials proved superior biocompatibility and promoted enhanced cell adhesion and proliferation with respect to human preosteoblast and osteosarcoma cell lines when compared to pristine titanium.

Nanomedicines: Nano based Drug Delivery Systems Challenges and Future of nanomedicines

Over the past ten years, the research and delivery of drugs has emerged as a rapidly expanding, highly capital-intensive, and demanding industry. This procedure is costly and time-consuming, and it has to deal with issues with rapid excretion, degradability, toxicity, low efficacy, biocompatibility, and low bioavailability. Nanomaterial are superior to conventional drug because they have remarkable qualities such as a high invasion rate, regulated, targeted, and gradual drug release, as well as easy receptor accessibility. Despite all of its importance, one of the main issues with different nanoparticles utilized as medication delivery systems is their toxicity. This review discusses the issue surrounding conventional drugs, the importance of nanomedicines in medication administration, and their potential for toxicity and also their future aspect that helps to improve health.

A new rapid-release SMA-activated micropump with incorporated microneedle arrays and polymeric nanoparticles for optimized transdermal drug delivery

Recent research in Transdermal drug delivery (TDD) systems has predominantly focused on microneedles (MNs) and nanoencapsulated drugs, which offer painless, gradual drug release but may not cater to quick-release drug demands. This study introduces an innovative approach to expedite the TDD process by merging a new rapid-release micropump, MNs, and nanoencapsulation into a modular framework. The fabrication and evaluation of a 3D printed shape memory alloy (SMA)-activated micropump combined with ibuprofen-loaded polymeric nanoparticles delivered via integrated MNs is thereby discussed. The system utilizes an SMA spring wire to actuate a loaded spring which drives an elastic membrane into a chamber integrated with an array of stereolithography (SLA) 3D printed MNs, facilitating painless injection into the dermis layer of the skin. The MNs array is optimized with finite element analysis (FEA) to minimize discomfort from the needles while maximizing the drug load into the skin. The system’s performance is characterized through high-speed camera imaging, and an average membrane speed of 0.28 m/s is developed. The system’s effectiveness is finally evaluated via a short time frame (5 minutes) ex vivo skin deposition experiment using Franz diffusion cells and rat skin, revealing almost twice the ibuprofen deposition in skin layers with polymeric nanoparticles compared to an untreated solution. The rapid response and demonstrated efficacy of this concept aims to provide a framework for potentially extending this application for transdermal insulin injection.

Implementing physics-based digital patient twins to tailor the switch of oral morphine to transdermal fentanyl patches based on patient physiology

Fentanyl transdermal patches are widely implemented for cancer-induced pain treatment due to the high potency of fentanyl and gradual drug release. However, transdermal fentanyl up-titration for opioid-naïve patients is difficult, which is why opioid treatment is often started with oral/iv morphine. Based on the daily dose of morphine, the initial dose of the fentanyl patch is decided upon. After reaching a stable level of pain, the switch is made from oral/iv morphine to transdermal fentanyl. There are standard calculation tools for transferring from oral/iv morphine to transdermal fentanyl, which is the same for all patients. By considering the variations in the physiology of the patients, a unique switching strategy cannot meet the needs of different patients. This study explores the outcome in terms of pain relief and minute ventilation during opioid therapy. For this, we used physics-based simulations on a virtually-generated population of patients, and we applied the same therapy to all patients. We could show that patients' physiology, such as gender, age, and weight, greatly impact the outcome of the therapy; as such, the correlation coefficient between pain intensity and age is 0.89, and the correlation coefficient between patient's weight and maximum plasma concentration of morphine and fentanyl is -0.98 and -0.97. Additionally, a different combination of the duration of overlap between morphine and fentanyl therapy with different doses of fentanyl was considered for the virtual patients to find the best opioid-switching strategy for each patient. We explored the impact of combining physiological features to determine the best-suited strategy for virtual patients. Our findings suggest that tailoring morphine and fentanyl therapy only based on a limited number of features is insufficient, and increasing the number of impactful physiological features positively influences the outcome of the therapy.

Novel melanin‐binding carbonic anhydrase II inhibitor for long‐acting topical glaucoma treatment

Aims/Purpose: We are developing new eye drop treatment for glaucoma with dosing frequency once a week by utilizing drug binding to ocular melanin. Carbonic anhydrase (CA) II enzyme inhibitors decrease intraocular pressure (IOP) and thus halt the progression of retinal damage by reducing the secretion of aqueous humour in the ciliary body. Since ciliary body is a melanin‐rich tissue, we hypothesize that long‐lasting CAII inhibition and IOP‐lowering effect may be achieved due to gradual drug release from melanin‐bound drug depot.Methods: Melanin binding affinity for about 30 novel CAII inhibitors was studied with microscale thermophoresis, and three structurally rather similar and equipotent molecules with different melanin binding properties were selected for in vivo efficacy studies. IOP‐lowering effect of these new molecules was studied with albino and pigmented rabbits with iCare® PRO rebound tonometer. For pharmacokinetic studies, the high melanin binding new CAI (molecule 184) was labelled with tritium, and the study was conducted with albino and pigmented rats with conventional methods. Bound drug was analysed from iris‐ciliary body pellet and unbound fraction from supernatants.Results: Melanin‐binding affinity of new CAII inhibitors varies from low or non‐binders (Kd > 650 μM) to high melanin binders (Kd < 65 μM). In vivo efficacy results show that the molecules decrease IOP in both albino and pigmented eyes at the level comparable with dorzolamide (Trusopt®). In pigmented eyes, melanin binding prolongs the effect of compound 184 even up to 2 weeks after single eye drop. In the pharmacokinetic rat study, molecule 184 shows remarkably prolonged tissue binding and high iris‐ciliary body exposure in pigmented eyes.Conclusions: After topical administration IOP‐lowering effect of high melanin‐binding CA II inhibitor is significantly prolonged in pigmented eyes.

Upconversion Nanoparticles Intercalated in Large Polymer Micelles for Tumor Imaging and Chemo/Photothermal Therapy.

Frontiers in theranostics are driving the demand for multifunctional nanoagents. Upconversion nanoparticle (UCNP)-based systems activated by near-infrared (NIR) light deeply penetrating biotissue are a powerful tool for the simultaneous diagnosis and therapy of cancer. The intercalation into large polymer micelles of poly(maleic anhydride-alt-1-octadecene) provided the creation of biocompatible UCNPs. The intrinsic properties of UCNPs (core@shell structure NaYF4:Yb3+/Tm3+@NaYF4) embedded in micelles delivered NIR-to-NIR visualization, photothermal therapy, and high drug capacity. Further surface modification of micelles with a thermosensitive polymer (poly-N-vinylcaprolactam) exhibiting a conformation transition provided gradual drug (doxorubicin) release. In addition, the decoration of UCNP micelles with Ag nanoparticles (Ag NPs) synthesized in situ by silver ion reduction enhanced the cytotoxicity of micelles at cell growth temperature. Cell viability assessment on Sk-Br-3, MDA-MB-231, and WI-26 cell lines confirmed this effect. The efficiency of the prepared UCNP complex was evaluated in vivo by Sk-Br-3 xenograft regression in mice for 25 days after peritumoral injection and photoactivation of the lesions with NIR light. The designed polymer micelles hold promise as a photoactivated theranostic agent with quattro-functionalities (NIR absorption, photothermal effect, Ag NP cytotoxicity, and Dox loading) that provides imaging along with chemo- and photothermal therapy enhanced with Ag NPs.

Composite double-layer microneedle loaded with traditional Chinese medicine for the treatment of androgenic alopecia

Androgenetic alopecia (AGA) is an androgen-mediated alopecia affected by both genes and hormones. Medication is a relatively common treatment. As a new drug delivery method, microneedles (MNs) can effectively break through the stratum corneum barrier, deliver drugs more efficiently, and achieve better therapeutic effects. In this study, we develop a composite double-layer MN through multi-step casting fabrication using a polydimethylsiloxane mold. The needle tip was fabricated by mixed solution of chitosan and polyvinylpyrrolidone which was loaded with Polygonum multiflorum extract, and the base layer was prepared by mixed solution of polyvinyl alcohol and polyvinylpyrrolidone. In vitro mechanical tests showed that the maximum load of a single tip of the drug-loaded MN was about 3.5 ​N, which met the mechanical requirements of skin puncture (>1 ​N). The drug release experiment showed that the MN could achieve gradual drug release. In the animal experiment, pigmentation and hair regrowth occurred earlier in the Polygonum multiflorum-MN (Pm-MN) group than in the other groups, and hair growth finally appeared in almost the entire area. Compared with the AGA model mice, mice in the Pm-MN group achieved an increase in the number and diameter of hair follicles. In conclusion, the Pm-MN is scientific and feasible for treating AGA.

Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients

Drug delivery platforms that allow for gradual drug release after intra-articular administration have become of much interest as a treatment strategy for osteoarthritis (OA). The aim of this study was to investigate the safety and efficacy of an intra-articular sustained release formulation containing celecoxib (CXB), a cyclooxygenase-2 (COX-2) selective inhibitor. Amino acid-based polyesteramide microspheres (PEAMs), a biodegradable and non-toxic platform, were loaded with CXB and employed in two in vivo models of arthritis: an acute inflammatory arthritis model in rats (n=12), and a randomized controlled study in chronic OA dog patients (n=30). In parallel, the bioactivity of sustained release of CXB was evaluated in monolayer cultures of primary dog chondrocytes under inflammatory conditions. Sustained release of CXB did not alleviate acute arthritis signs in the rat arthritis model, based on pain measurements and synovitis severity. However, in OA dog patients, sustained release of CXB improved limb function as objective parameter of pain and quality of life based on gait analysis and owner questionnaires. It also decreased pain medication dependency over a 2-month period and caused no adverse effects. Prostaglandin E2 levels, a marker for inflammation, were lower in the synovial fluid of CXB-treated dog OA patients and in CXB-treated cultured dog chondrocytes. These results show that local sustained release of CXB is less suitable to treat acute inflammation in arthritic joints, while safe and effective in treating pain in chronic OA in dogs.

Towards Drug Release Dynamics from a Multifractal Perspective of Motion

Abstract A new mathematical method in the drug release dynamics is proposed using Scale Relativity Theory. Our method is completely different than the standard one, because the variables through which we can describe the release dynamics are non-differentiable mathematical functions (i.e. mathematicals functions both dependent of spatial and time coordinates, and also of scale resolutions). In such context, the scale resolution is correlated with drug release degree so that various drug release regimes can be highlighted (gradual drug release, saturation, decay of polymer matrix etc.).

Application of G-quadruplex aptamer conjugated MSNs to deliver ampicillin for suppressing S. aureus biofilm on mice bone

Staphylococcus aureus is a common bacterial agent of biofilm formation in medical environments. The formed biofilm of this bacterium in bone tissue is one of the main causes of osteomyelitis, which is a serious health issue. Due to the importance of this infection after traumatic injuries or surgical intervention, it is necessary to develop a system that could release the antibiotics at the site of injury, specifically and gradually. The current study aimed to develop a nanosystem composed of single-stranded G-quadreplex DNA aptamer as the bio-recognition element, mesoporous silica nanoparticles (MSNs) as the carrier for gradual drug release, and Ampicillin as the cargo to be delivered to the site of infection. In silico methods were used to select an optimum binding aptamer against protein A of S. aureus . The binding of aptamer was confirmed via gel retardation assay, DLS, and Zeta potential analyses. The loading of the drug was confirmed by the FTIR method, and the drug release investigation showed almost 30 % of drug release via 48 h dialysis assay. The acquired results from the biofilm suppression assay indicated that this system provides a significant inhibitory effect against the S. aureus biofilm and has a high potential for the desired drug release to prevent the formation of biofilm, and could destroy the biofilm on the mice bone. The results of the MTT assay proved that this system does not pose a significant toxicity thread for MCF-7 cell viability, as a model for eukaryotic cells. In vivo studies are required to further confirm the efficacy of this system against S. aureus biofilm on bone.

Gradual Drug Release Membranes and Films Used for the Treatment of Periodontal Disease.

Periodontitis is an inflammatory disease that, if not treated, can cause a lot of harm to the oral cavity, to the patients’ quality of life, and to the entire community. There is no predictable standardized treatment for periodontitis, but there have been many attempts, using antibiotics, tissue regeneration techniques, dental scaling, or root planning. Due to the limits of the above-mentioned treatment, the future seems to be local drug delivery systems, which could gradually release antibiotics and tissue regeneration inducers at the same time. Local gradual release of antibiotics proved to be more efficient than systemic administration. In this review, we have made a literature search to identify the articles related to this topic and to find out which carriers have been tested for drug release as an adjuvant in the treatment of periodontitis. Considering the inclusion and exclusion criteria, 12 articles were chosen to be part of this review. The selected articles indicated that the drug-releasing carriers in periodontitis treatment were membranes and films fabricated from different types of materials and through various methods. Some of the drugs released by the films and membranes in the selected articles include doxycycline, tetracycline, metronidazole, levofloxacin, and minocycline, all used with good outcome regarding their bactericide effect; BMP-2, Zinc–hydroxyapatite nanoparticles with regenerative effect. The conclusion derived from the selected studies was that gradual drug release in the periodontal pockets is a promising strategy as an adjuvant for the treatment of periodontal disease.

Fabrication and Evaluation of Controlled Release Transdermal Drug Delivery System of Carvedilol using Design Expert Software for the Management of Hypertension

Published on:August 2022Journal of Young Pharmacists, 2022; 14(3):295-301Original Article | doi:10.5530/jyp.2022.14.58 Authors: Saurabh Maan1, Roop Krishen Khar2, Rupa Mazumder3,*, Nishant Yadav1, Urooj Ahmed Khan4,* 1Department of Pharmaceutics, B.S. Anangpuria Institute of Pharmacy, Faridabad, Haryana, INDIA. 2Department of Pharmaceutics, B.S. Anangpuria Educational Institute, Faridabad, Haryana, INDIA. 3Department of Pharmacy, Noida Institute of Engineering and Technology, Greater Noida, Uttar Pradesh, INDIA. 4Department of Pharmaceutics, School of Medical and Allied Sciences, K.R Mangalam University, Sohna Road, Gurugram, Haryana, INDIA. Abstract: Objectives: Design, development and characterization of controlled release transdermal drug delivery system of carvedilol using Design Expert® software for managing hypertension. Materials and Methods: CV undergoes extensive first-pass metabolism due to low oral bioavailability approx ~24% and biological half-life ~6 hr. Available CV preparations have drawback of poor patient compliance due to increase in dosing frequency and making the therapy less effective. Phospholipid E80, glycerol and cholesterol were used for preparing CVGs via film hydration technique. Optimization was done using Central Composite Design under Design Expert software. While PVP and EC in a ratio of 4:1 in chloroform (5 mL) with plasticizer dibutyl phthalate (30%) were used for preparing Matrix type transdermal patch containing CVGs. Results: Optimized CVGs showed 115.7 nm particle size, and -16.4 mV zeta potential. TEM analysis also showed similar vesicle size and reveals globular structure of CVGs. Nearly 0.31 mm thickness, 0.14 % g weight variation, 99.13% flatness and 98.72% drug content was found in Matrix type transdermal patch having CVGs Transdermal patch with Franz diffusion cell showed approx. 90% release upto 48 hr during in-vitro permeation studies. In-vivo pharmacological assessment was done for efficacy estimation of GVs transdermal patch by N-nitro-L-arginine methyl ester which produced significant hypertension in rats. The application of CVGs transdermal patch resulted in a gradual decrease in BP, with the maximum effect from the patch observed at 10 hr (p < 0.001), the effect continued for 48 hr clearly indicating the gradual release of drug by transdermal patch for a long period. Conclusion: Developed novel transdermal patch having CV loaded glycerosomes may be considered as a promising approach for controlled release of drug with effective hypertension management. Keywords: Transdermal, Carvedilol, Design Expert, Glycerosomes, Hypertension, CCD.

580 Biodegradable bioadhesive nanoparticle delivery of chemotherapy for the treatment of cutaneous malignancies

Encapsulation of chemotherapeutic agents within biodegradable nanoparticles (NP) allows for gradual drug release from the polylactic acid core. Bioadhesive, degradable NPs can be retained at the site of administration, maximizing local effects while minimizing systemic side effects. Our bioadhesive NP (BNP) loaded with chemotherapy have previously been proven efficacious in the treatment of murine PDVC57 squamous cell carcinoma (SCC) tumors, with increased intratumoral (i.t.) retention of the active agent.

Investigating the Potential of Ethyl Cellulose and a Porosity-Increasing Agent as a Carrier System for the Formulation of Amorphous Solid Dispersions.

In the present work, an insoluble polymer, i.e., ethyl cellulose (EC), was combined with the water-soluble polyvinylpyrrolidone (PVP) as a carrier system for the formulation of amorphous solid dispersions. The rationale was that by conjoining these two different types of carriers a more gradual drug release could be created with less risk for precipitation. Our initial hypothesis was that upon contact with the dissolution medium, PVP would be released, creating a porous EC matrix through which the model drug indomethacin could diffuse. On the basis of observations of EC as a coating material, the effect of the molecular weight of PVP, and the ratio of EC/PVP on the miscibility of the polymer blend, the solid state of the solid dispersion and the drug release from these solid dispersions were investigated. X-ray powder diffraction, modulated differential scanning calorimetry, and solid-state nuclear magnetic resonance were used to unravel the miscibility and solid-state properties of these blends and solid dispersions. Solid-state nuclear magnetic resonance appeared to be a crucial technique for this aspect as modulated differential scanning calorimetry was not sufficient to grasp the complex phase behavior of these systems. Both EC/PVP K12 and EC/PVP K25 blends were miscible over the entire composition range, and addition of indomethacin did not alter this. Concerning the drug release, it was initially thought that more PVP would lead to faster drug release with a higher probability that all of the drug molecules would be able to diffuse out of the EC network as more pores would be created. However, this view on the release mechanism appeared to be too simplistic as an optimum was observed for both blends. On the basis of this work, it could be concluded that drug release from this complex ternary system was affected not only by the ratio of EC/PVP and the molecular weight of PVP but also by interactions between the three components, the wettability of the formulations, and the viscosity layer that was created around the particles.

Development and Optimization of Chitosan-Hydroxypropyl Methylcellulose In Situ Gelling Systems for Ophthalmic Delivery of Bupivacaine Hydrochloride

The aim of this study was the development and optimization of chitosan and hydroxypropyl methylcellulose (HPMC) in situ gelling systems, loaded with bupivacaine hydrochloride for topical ocular administration. This study is based on the properties of two polymers: chitosan, which has mucoadhesive action and is a pH-sensitive polymer, but also the cellulose derivative hydroxypropyl methylcellulose, a thermosensitive polymer which has mucoadhesive properties and increases the viscosity of systems. The analysis and optimization of in situ gelling systems were performed based on an experimental design and response surface methodology. The following formulation parameters were considered: X1 = chitosan concentration (0.5%, 1%), X2 = HPMC E 5 LV concentration (2%, 5%) and X3 = Chitosan/HPMC E 5 LV ratio (1/1, 2/1). In addition, the parameters to be optimized were represented by the contact angle (CA (°)), viscosity and cumulative percentage of bupivacaine hydrochloride released in vitro. The results indicate that the designed in situ gelling systems are suitable for bupivacaine prolonged ophthalmic release and overcome the principal disadvantages of the liquid’s ocular formulations. An immediate therapeutic effect corresponding to ocular anesthetic installation was assured in the first stage: burst bupivacaine release. In the second phase, the gradual drug release was assured for over 6 h. This drug release profile, together with the corresponding rheological profile and a collection of superficial properties for good ocular adhesion balanced with an adequate hydrophilic character, assured the desired quality of the attributes for the proposed systems. The system, based on chitosan 1%, HPMC E 5 LV 5% and a 1/1 polymer ratio, could be a solution for the proposed formulation of in situ gelling colloidal systems, since the viscosity of the system was within the range of the optimal viscosity of the eye, and the amount of bupivacaine hydrochloride released after 6 h was the highest at 69.55%.

Bacterial navigation for tumor targeting and photothermally-triggered bacterial ghost transformation for spatiotemporal drug release

Cancer chemotherapy is confronted with challenges regarding the effective delivery of chemotherapeutics into tumor cells after systemic administration. Herein, we propose a strategy to load drugs into probiotic E. coli Nissle 1917 (EcN) for self-guided navigation to tumor tissues and subsequently release the drugs with in situ transformation into bacterial ghosts (BGs). Chemotherapeutic agent 5-fluorouracil (FU) and macrophage phenotype regulator zoledronic acid (ZOL) are loaded into EcN through electroporation, followed by decoration of Au nanorods on the ECN surface to construct EcNZ/F@Au. High loading levels of 5FU (8.8%) and ZOL (10.5%) are achieved as well as high retention rates of bacterial viability (87%) and motion velocity (88%). Under near infrared (NIR) illumination the photothermal effect of Au nanorods elevates the local temperature to induce the transformation of live EcN into BGs. The created transmembrane channels initiate the gradual drug release from BGs, thus representing the first attempt to control the drug release via a biological evolution. An intermittent NIR illumination causes stepwise increases in the BG formation and drug release, which could implement an external on-off control and spatiotemporal drug release. Self-guided motion of EcN promotes efficient extravasation across blood vessels and preferential accumulation of drugs in tumors. In addition to the chemotherapeutic effect of FU, the local release of ZOL from EcNZ/F@Au enhances valid polarization of tumor-associated macrophages toward the M1 phenotype and an effective production of proinflammatory cytokines, leading to a synergistic efficacy on tumor growth inhibition. Thus, this study demonstrates a feasible strategy to integrate chemotherapy, immunotherapy, and photothermal effects in a concise manner for effective cancer treatment with few side effects. Statement of SignificanceBacteria are capable to trace and colonize in hypoxic tumor tissues. Bacterial drug carriers indicate limitations in efficient drug loading and effective release modulation. Herein, we propose a strategy to load drugs into bacteria for self-guided delivery and subsequently release the drugs in tumors with in situ transformation into bacterial ghost (BGs). Drugs are loaded into live bacteria through electroporation and Au nanorods are decorated on the bacterial surface, wherein the photothermal effect, chemotherapy, and immunotherapy are integrated in a concise manner. NIR illmumination of Au nanorods elevates the local temparature, induces the BG tranformation, and activates the spatiotemporal drug release, representing the first attempt of release modulation via a biological evolution.

Immune Cell Membrane-Coated Biomimetic Nanoparticles for Targeted Cancer Therapy.

Nanotechnology has provided great opportunities for managing neoplastic conditions at various levels, from preventive and diagnostic to therapeutic fields. However, when it comes to clinical application, nanoparticles (NPs) have some limitations in terms of biological stability, poor targeting, and rapid clearance from the body. Therefore, biomimetic approaches, utilizing immune cell membranes, are proposed to solve these issues. For example, macrophage or neutrophil cell membrane coated NPs are developed with the ability to interact with tumor tissue to suppress cancer progression and metastasis. The functionality of these particles largely depends on the surface proteins of the immune cells and their preserved function during membrane extraction and coating process on the NPs. Proteins on the outer surface of immune cells can render a wide range of activities to the NPs, including prolonged blood circulation, remarkable competency in recognizing antigens for enhanced targeting, better cellular interactions, gradual drug release, and reduced toxicity in vivo. In this review, nano-based systems coated with immune cells-derived membranous layers, their detailed production process, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, future perspectives and challenges for their clinical translation are also presented.