Combined Drug Delivery Research Articles

Cover Feature: A Nanoplatform Based on Pillar[5]arene Nanovalves for Combined Drug Delivery and Enhanced Antitumor Activity (Chem. Eur. J. 13/2024)

Cover Feature: A Nanoplatform Based on Pillar[5]arene Nanovalves for Combined Drug Delivery and Enhanced Antitumor Activity (Chem. Eur. J. 13/2024)

Nanoparticles loaded with β-Lapachone and Fe3+ exhibit enhanced chemodynamic therapy by producing H2O2 through cascaded amplification

The rapid, irreversible change of active Fe2+ to inactive Fe3+ after the Fenton reaction occurring reduces the chemodynamic therapeutic (CDT) effect. Therefore, manipulation of the tumor microenvironment to provide sufficient hydrogen peroxide (H2O2) while maintaining metal ion catalyst activity is critical for effective CDT. Here, β-Lapachone (LPC) was loaded by mesoporous silica nanoparticles (MSNs) and coated with polydopamine (PDA) to further chelate Fe3+ and link aptamer AS1411, and a pH-controlled released, chemotherapy-photothermal therapy (PTT)-enhanced CDT-small molecule therapy combination drug delivery system with passive and active tumor targeting was engineered (designated as β-LPC@MSN@PDA/Fe3+-AS1411, LMPFA). The results showed that LFMPA nanoparticles massively accumulated in tumor tissues to achieve tumor targeting through AS1411 mediating and enhanced permeability and retention (EPR) effect. Subsequently, PDA released Fe3+ and LPC through acid response to exhibited CDT and chemotherapeutic therapy. Meanwhile, the photothermal effect of PDA promoted the release of LPC from the pores of MSN. LPC exerted chemotherapy effect and cyclically producing of H2O2 by the catalysis of NQO1, which enhanced the CDT activated by Fe3+. In addition, while serving as a targeted ligand, AS1411 could also exhibit a small molecule therapeutic effect by binding to nucleoli of tumor cells. This unique nano delivery system achieved the combination of chemotherapy, PTT, enhanced CDT and small molecule therapy, and fought against malignant tumors synergistically through multi-target and multi-dimension.

A Nanoplatform Based on Pillar[5]arene Nanovalves for Combined Drug Delivery and Enhanced Antitumor Activity.

Modern nanodrug delivery technologies offer new approaches in the fight against cancer. However, due to the heterogeneity of tumors and side effects of anticancer drugs, monotherapies are less effective. Herein, we report a novel pH and light dual-responsive nanodrug delivery platform. The platform was formed by sulfonate-modified gold nanoparticles loaded with the anticancer drugs doxorubicin (DOX) and glucose oxidase (GOx) and then covered by water-soluble pillar[5]arene as a nanovalve. The nanovalve formed by the host-guest interaction between pillar[5]arene and the sulfonic acid group grafted onto the gold nanoparticle increased the drug loading capacity of the nanoplatform and enabled sustained release of the drug in a simulated weakly acidic tumor environment. The released GOx can consume intracellular glucose, namely, starvation therapy, while the generated hydrogen peroxide can further kill tumor cells, complementing DOX chemotherapy. Gold nanoparticles have good photothermal conversion ability and can enhance the drugs release rate under specific wavelengths of light irradiation. The results of in vitro and in vivo experiments showed that this novel nanodrug delivery platform has good biocompatibility and better therapeutic efficacy relative to monotherapy. This study successfully developed a combined chemo/starvation therapy strategy with good tumor suppression, providing a new approach for cancer treatment.

Leveraging Technology for Vestibular Assessment and Rehabilitation in the Operational Environment: A Scoping Review.

The vestibular system, essential for gaze and postural stability, can be damaged by threats on the battlefield. Technology can aid in vestibular assessment and rehabilitation; however, not all devices are conducive to the delivery of healthcare in an austere setting. This scoping review aimed to examine the literature for technologies that can be utilized for vestibular assessment and rehabilitation in operational environments. A comprehensive search of PubMed was performed. Articles were included if they related to central or peripheral vestibular disorders, addressed assessment or rehabilitation, leveraged technology, and were written in English. Articles were excluded if they discussed health conditions other than vestibular disorders, focused on devices or techniques not conducive to the operational environment, or were written in a language other than English. Our search strategy yielded 32 articles: 8 articles met our inclusion and exclusion criteria whereas the other 24 articles were rejected. There is untapped potential for leveraging technology for vestibular assessment and rehabilitation in the operational environment. Few studies were found in the peer-reviewed literature that described the application of technology to improve the identification of central and/or peripheral vestibular system impairments; triage of acutely injured patients; diagnosis; delivery and monitoring of rehabilitation; and determination of readiness for return to duty. This scoping review highlighted technology for vestibular assessment and rehabilitation feasible for use in an austere setting. Such technology may be leveraged for prevention; monitoring exposure to mechanisms of injury; vestibular-ocular motor evaluation; assessment, treatment, and monitoring of rehabilitation progress; and return-to-duty determination after vestibular injury. The future of vestibular assessment and rehabilitation may be shaped by austere manufacturing and 3D printing; artificial intelligence; drug delivery in combination with vestibular implantation; organ-on-chip and organoids; cell and gene therapy; and bioprinting.

Curcumin Nanocarriers with a Focus on Cellular Uptake Studies – An Innovative Cancer Therapy

Once a dye, curcumin (CUR) has transformed into a versatile therapeutic agent with antioxidative, anti-inflammatory, and anticancer properties. Despite its potent anticancer effects, CUR encounters challenges such as poor solubility and a short circulation half-life. To address this, researchers utilize nanocarriers like nanoparticles, liposomes, and micelles for efficient CUR delivery. With its multifaceted anticancer activity, CUR holds promise as a cancer therapeutic. Recent studies concentrate on crafting nanocarriers tailored for size, charge, and functionalization, offering adaptable tools for combinational cancer therapy. The synergistic combination of CUR with chemotherapy, magnetic nano hyperthermia, or photodynamic therapy amplifies the efficacy of malignancy treatment. The investigation into CUR-loaded nanocarriers, whether used alone or in combination with other modalities, aims to enhance cancer treatment outcomes, highlighting the diverse potential of curcumin in contemporary therapeutic strategies. This research underscores the importance of combinational drug delivery therapies, providing a renewed perspective on the versatile applications of curcumin in modern medicine.

Visible light and pH-responsive star copolymer and doxorubicin-polymer conjugate micelles for combination drug delivery and bioimaging

Amphiphilic 3-arm star copolymer containing visible light-cleavable BODIPY group and pH-responsive imine bonds at the junction of hydrophilic poly(ethylene glycol) (PEG) and two poly(ε-caprolactone) (PCL) arms was synthesized by the combination of ring-opening polymerization (ROP) and click chemistry. The formation and stimuli-responsive disruption of micelles were analyzed using dynamic light scattering and transmission electron microscopy. Dual stimuli-responsive release of anticancer drugs Doxorubicin (Dox) and Camptothecin (CPT) from the micelles was studied. Micellar assemblies containing Dox conjugated to PEG-BODIPY through imine bonds were prepared and controlled release of Dox in response to visible light and pH was shown. CPT and Dox-loaded star copolymer micelles as well as CPT loaded Dox-conjugated micelles were used in cellular uptake studies on MDA-MB 231 cells, and the synergistic effect of the two stimuli on the release of the two drugs was demonstrated inside the cells. Micellar assemblies also showed excellent bioimaging properties in the cellular uptake studies.

Combination of mangiferin and T0901317 targeting autophagy promotes cholesterol efflux from macrophage foam cell in atherosclerosis

BackgroundThe synthetic liver X receptor ligand (LXR) T0901317 (T0) has been reported to attenuate atherosclerosis (AS) without hyperglyceridemia due to innovative drug combination or nano-sized drug delivery. Given the key roles of mangiferin (MGF) in lipid metabolism and atherogenesis, it is critical to investigate progression of atherosclerotic lesion after combined treatment of MGF and T0.MethodsAtherosclerotic plaque formation and hepatic lipid accumulation were compared in Apoe−/− mice among T0 and/or MGF treatment. The in vitro functions of MGF and T0 were analyzed by Oil-red O staining, cholesterol efflux assay, transmission electron microscopy and western blot analyses with or without acetylated low density lipoprotein.ResultsThe combination therapy are effective regulators for atherosclerotic plaque formation in Apoe−/− mice, due to upregulation of ABCA1 and ABCG1 induced by LXR activation. Subsequently, we identified autophagy promoted by MGF and T0 treatment establishes a positive feedback loop that increases cholesterol efflux, resulted from LXRα activation. Under atherogenic conditions, the autophagy inhibitor CQ abolished the enhancement effect on cholesterol outflow of MGF and T0. Mechanically, MGF and T0 promotes LXRα and mTOR/AMPK signaling cascade in macrophage, and promotes AMPK signaling cascade in hepatocyte, leading to lipid metabolic homeostasis.ConclusionsAltogether, our findings reveal that MGF and T0 engages in AS therapy without side effects by activating AMPK-dependent autophagy to promote macrophage cholesterol efflux, and MGF might serve as a natural compound to assist T0 in AS via targeting autophagy.

Nanotechnology-assisted combination drug delivery: a progressive approach for the treatment of acute myeloid leukemia.

Acute myeloid leukemia (AML), a heterogeneous hematopoietic cancer prevalent in adults, has been a leading cause of leukemia-associated deaths for decades. Despite advancements in understanding its pathology and pharmacological targets, therapeutic strategies have seen minimal change. The standard treatment, combining cytarabine and anthracycline, has persisted, accompanied by challenges such as pharmacokinetic issues and non-specific drug delivery, leading to severe side effects. Nanotechnology offers a promising solution through combination drug delivery. FDA-approved CPX351 (VYXEOS™) a liposomal formulation delivering doxorubicin and cytarabine, exemplifies enhanced therapeutic efficacy. Ongoing research explores various nanocarriers for delivering multiple bioactives, addressing drug targeting, pharmacokinetics and chemoresistance. This review highlights nanotechnology-based combination therapies for the effective management of AML, presenting a potential breakthrough in leukemia.

Magnetic iron oxide nanogels for combined hyperthermia and drug delivery for cancer treatment.

Hyperthermia and chemotherapy represent potential modalities for cancer treatments. However, hyperthermia can be invasive, while chemotherapy drugs often have severe side effects. Recent clinical investigations have underscored the potential synergistic efficacy of combining hyperthermia with chemotherapy, leading to enhanced cancer cell killing. In this context, magnetic iron oxide nanogels have emerged as promising candidates as they can integrate superparamagnetic iron oxide nanoparticles (IONPs), providing the requisite magnetism for magnetic hyperthermia, with the nanogel scaffold facilitating smart drug delivery. This review provides an overview of the synthetic methodologies employed in fabricating magnetic nanogels. Key properties and designs of these nanogels are discussed and challenges for their translation to the clinic and the market are summarised.

Advances in drug delivery-based therapeutic strategies for renal fibrosis treatment.

Renal fibrosis is the result of all chronic kidney diseases and is becoming a major global health hazard. Currently, traditional treatments for renal fibrosis are difficult to meet clinical needs due to shortcomings such as poor efficacy or highly toxic side effects. Therefore, therapeutic strategies that target the kidneys are needed to overcome these shortcomings. Drug delivery can be attained by improving drug stability and addressing controlled release and targeted delivery of drugs in the delivery category. By combining drug delivery technology with nanosystems, controlled drug release and biodistribution can be achieved, enhancing therapeutic efficacy and reducing toxic cross-wise effects. This review discusses nanomaterial drug delivery strategies reported in recent years. Firstly, the present review describes the mechanisms of renal fibrosis and anti-renal fibrosis drug delivery. Secondly, different nanomaterial drug delivery strategies for the treatment of renal injury and fibrosis are highlighted. Finally, the limitations of these strategies are also discussed. Investigating various anti-renal fibrosis drug delivery strategies reveals the characteristics and therapeutic effects of various novel nanosystem-derived drug delivery approaches. This will serve as a reference for future research on drug delivery strategies for renal fibrosis treatment.

Microneedle-Assisted Transfersomes as a Transdermal Delivery System for Aspirin.

Transdermal drug delivery systems offer several advantages over conventional oral or hypodermic administration due to the avoidance of first-pass drug metabolism and gastrointestinal degradation as well as patients' convenience due to a minimally invasive and painless approach. A novel transdermal drug delivery system, comprising a combination of transfersomes with either solid silicon or solid polycarbonate microneedles has been developed for the transdermal delivery of aspirin. Aspirin was encapsulated inside transfersomes using a "thin-film hydration sonication" technique, yielding an encapsulation efficiency of approximately 67.5%. The fabricated transfersomes have been optimised and fully characterised in terms of average size distribution and uniformity, surface charge and stability (shelf-life). Transdermal delivery, enhanced by microneedle penetration, allows the superior permeation of transfersomes into perforated porcine skin and has been extensively characterised using optical coherence tomography (OCT) and transmission electron microscopy (TEM). In vitro permeation studies revealed that transfersomes enhanced the permeability of aspirin by more than four times in comparison to the delivery of unencapsulated "free" aspirin. The microneedle-assisted delivery of transfersomes encapsulating aspirin yielded 13-fold and 10-fold increases in permeation using silicon and polycarbonate microneedles, respectively, in comparison with delivery using only transfersomes. The cytotoxicity of different dose regimens of transfersomes encapsulating aspirin showed that encapsulated aspirin became cytotoxic at concentrations of ≥100 μg/mL. The results presented demonstrate that the transfersomes could resolve the solubility issues of low-water-soluble drugs and enable their slow and controlled release. Microneedles enhance the delivery of transfersomes into deeper skin layers, providing a very effective system for the systemic delivery of drugs. This combined drug delivery system can potentially be utilised for numerous drug treatments.

Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry.

Extracellular vesicles (EVs) are lipid bilayer structures released by all cells that mediate cell-to-cell communication via the transfer of bioactive cargo. Because of the natural origin of EVs, their efficient uptake by recipient cells, capacity to stabilize and transport biomolecules and their potential for cell/tissue targeting and preferential uptake by cancer cells, they have enormous potential for bioengineering into improved and targeted drug delivery systems. In this work, we investigated the use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a tool to measure the loading of platinum-based chemotherapeutic agents. The EV loading of oxaliplatin via co-incubation was demonstrated, and LA-ICP-MS imaging showed greater efficiency of delivery to colorectal cancer cells compared to free oxaliplatin, leading to enhanced cytotoxic effect. Further, the impact of EV co-loading with a porphyrin (C5SHU, known as 'C5') photosensitizer on oxaliplatin delivery was assessed. Fluorescence analysis using nano-flow cytometry showed dose-dependent EV loading as well as a trend towards the loading of larger particles. Exposure of OXA-C5-EV-treated colorectal cancer cells to light indicated that delivery was enhanced by both light exposure and porphyrins, with a synergistic effect on cell viability observed between oxaliplatin, EVs and light exposure after the delivery of the co-loaded EVs. In summary, this work demonstrates the utility of LA-ICP-MS and mass spectrometry imaging in assessing the loading efficiency and cellular delivery of platinum-based therapeutics, which would also be suitable for agents containing other elements, confirms that EVs are more efficient at delivery compared to free drugs, and describes the use of light exposure in optimizing delivery and therapeutic effects of EV-mediated drug delivery both in combination and independently of porphyrin-based photosensitizers.

An androgenetic alopecia remedy based on marine collagen peptide-incorporated dissolving microneedles

Given that current androgenetic alopecia (AGA) medications have adverse effects such as sexual dysfunction and drug dependence, researchers are actively exploring natural bioactive ingredients and innovative approaches (e.g., transdermal drug delivery systems) to effectively combat hair loss with minimal side effects. Herein, we develop a new transdermal drug delivery system incorporating globefish skin collagen peptides with dissolving microneedles (GSCPs-MNs) for hair regrowth. These microneedles generate skin micro-wounds upon application, which not only improves the efficiency of bioactive ingredients delivery, but also stimulates signals involved in hair follicle (HF) regeneration. Our in vivo study shows that minimally invasive implanted GSCPs-MNs are more effective than topical GSCPs in reducing inflammation and promoting collagen formation. Additionally, the upregulation of vascular markers including VEGF and CD31 alongside the downregulation of TNF-α, IL-1β, and malondialdehyde (MDA) index indicate that GSCPs-MNs can significantly alleviate inflammation and oxidation, as well as promoting vascularization and HF functionalization. Overall, our findings suggest that GSCPs-MNs can effectively promote hair regrowth in AGA mice, which offer excellent prospects for the development of new therapeutics and cosmetic supplements for hair loss, along with the combined drug delivery optimization, which could alleviate hair loss in patients with AGA.

Improved Reversion of Calcifications in Porcine Aortic Heart Valves Using Elastin-Targeted Nanoparticles.

Calcified aortic valve disease in its final stage leads to aortic valve stenosis, limiting cardiac function. To date, surgical intervention is the only option for treating calcific aortic valve stenosis. This study combined controlled drug delivery by nanoparticles (NPs) and active targeting by antibody conjugation. The chelating agent diethylenetriaminepentaacetic acid (DTPA) was covalently bound to human serum albumin (HSA)-based NP, and the NP surface was modified using conjugating antibodies (anti-elastin or isotype IgG control). Calcification was induced ex vivo in porcine aortic valves by preincubation in an osteogenic medium containing 2.5 mM sodium phosphate for five days. Valve calcifications mainly consisted of basic calcium phosphate crystals. Calcifications were effectively resolved by adding 1-5 mg DTPA/mL medium. Incubation with pure DTPA, however, was associated with a loss of cellular viability. Reversal of calcifications was also achieved with DTPA-coupled anti-elastin-targeted NPs containing 1 mg DTPA equivalent. The addition of these NPs to the conditioned media resulted in significant regression of the valve calcifications compared to that in the IgG-NP control without affecting cellular viability. These results represent a step further toward the development of targeted nanoparticular formulations to dissolve aortic valve calcifications.

A dual-functional nanomedicine combining fluorinated antisense oligonucleotide with chemotherapeutic drug for synergistic gene-chemo tumor treatment

The synergistic anti-tumor therapy based on chemotherapeutic drugs and gene drugs has become a new direction of tumor treatment. However, the significantly distinct physicochemical properties and the unbalanced coordinate proportion of chemotherapeutic and genetic drugs limit the actual therapeutic efficiency of the combined drug delivery strategy. Herein, we developed a simple method to self-assemble the fluorine atom-modified antisense oligonucleotide (2′F-G1319) with chemotherapeutic pirarubicin (THP) to form the carrier-free nanomedicines (2′F-G1319/THP NMs), which could efficaciously achieve the synergistic gene therapy and chemotherapy. In this study, 2′F-G1319 and THP could be self-assembled to form uniform nanoparticles through enhanced intermolecular interactions after G1319 was modified with the fluorine atom. Both in-vitro and in-vivo experiments verified that 2′F-G1319/THP NMs exhibited significant synergistic anti-tumor effects with high biostability and biocompatibility. Owing to the simple and universal synthesis process, our constructed self-assembled nanomedicine provides a promising opportunity for the wide applications of nanomedicines and is expected to realize more effective synergistic anti-tumor therapy without the addition of non-therapeutic excipients

Stimuli-responsive nanoparticles delivered by a nasal-brain pathway alleviate depression-like behavior through extensively scavenging ROS.

Depression is one of the most common mental diseases, which seriously affects patients' physical and mental health. Emerging evidence has indicated that oxidative stress (OS) is a major cause of neurodegeneration involved in the pathogenesis of depression. Consequently, targeted reactive oxygen species (ROS) elimination is regarded as a promising strategy for efficient depression therapy. In addition, insufficient brain drug delivery is the main obstacle to depression therapy owing to the presence of the blood-brain barrier (BBB). To achieve the goals of bypassing the BBB and promoting antioxidant therapy for depression, a broad-spectrum ROS scavenging NPs was rationally designed through a nasal-brain pathway developed for combined ROS scavenging and brain drug delivery. A hexa-arginine (R6) modified ROS-responsive dextran (DEX) derivate was synthesized for antidepressant olanzapine (Olz) and H2 donor amino borane (AB) loading to prepare Olz/RDPA nanoparticles (NPs). Subsequently, the NPs were dispersed into a thermoresponsive hydrogel system based on poloxamer. In vitro and in vivo results demonstrated that Olz/RDPA in situ thermoresponsive hydrogel system could effectively deliver NPs to the brain via the nasal-brain pathway and alleviate depression-like behaviors through combined ROS depletion and inhibition of 5-HT dysfunction of the oxidative stress-induced. The proposed ROS-scavenging nanotherapeutic would open a new window for depression treatment. STATEMENT OF SIGNIFICANCE: ROS is an innovative therapeutic target involving the pathology of depression whereas targeted delivery of ROS scavenging has not been achieved yet. In the current study, ROS-responsive nanoparticles (Olz/RDPA NPs) were prepared and dispersed in a thermosensitive hydrogel for delivery through the nasal-brain pathway for the treatment of depression. Sufficient ROS depletion and improvement of delivery capacity by the nasal-brain pathway effectively could reverse oxidative stress and alleviate depressive-like behavior. Collectively, these nanoparticles may represent a promising strategy for the treatment of depression.

Insight with Crystallization, Quantum Computation, Hirshfeld, ELF/LOL and Molecular Docking of Syringic Acid Nicotinamide Cocrystal as Potent Mycobacterium Tuberculosis Inhibitor

Tuberculosis (TB) is a recurring and progressive illness with a high global death rate. MycobacteriumTB drug resistance is a serious impediment to allelopathy therapy. Contemplating combinatorial drug delivery (pharmaceutical cocrystal) as anti-TB medicines targeting Mycobacterium tuberculosis’s active site can be an alternative strategy. The syringic acid nicotinamide (SYNI) cocrystal was synthesized in this work through slow evaporation technique and was examined based on quantum chemical calculations, Hirshfeld analysis, electron localization analysis and molecular docking. The intended vibrational wavenumbers were allocated a PED value and related with experimental frequencies. The UV–Visible absorption spectra of the cocrystal in the liquid phase (ethanol) were revealed as [Formula: see text]* electronic transitions. The HOMO–LUMO values, band gap, molecular electrostatic potential and Mulliken atomic charge distribution of the molecule were evaluated to estimate its stability and molecular reactivity. The molecule’s second-order perturbation energy [Formula: see text] standards were determined by means of natural bond orbital analysis, and potential reactive site was assessed using local reactivity descriptors. Hirshfeld analysis revealed that H…H (44.9%), O…H/H…O (39.3%), C…H/H…C (6.1%), N…H/H…N (5.3%) and C…C (2.4%) have the major percentage contributions from the most significant interactions. The topological features of the SYNI cocrystal were assessed through electron localization function based on color gradient. The binding ability of SYNI cocrystal with the Mycobacterium tuberculosis associated proteins was evaluated through docking and their binding scores fall between the range of −9.1 kcal/mol and −10.8 kcal/mol, which confirms the better binding ability and makes SYNI cocrystal a potent medication against TB.

The Therapeutic Potential of Natural Dietary Flavonoids against SARS-CoV-2 Infection.

The exploration of non-toxic and cost-effective dietary components, such as epigallocatechin 3-gallate and myricetin, for health improvement and disease treatment has recently attracted substantial research attention. The recent COVID-19 pandemic has provided a unique opportunity for the investigation and identification of dietary components capable of treating viral infections, as well as gathering the evidence needed to address the major challenges presented by public health emergencies. Dietary components hold great potential as a starting point for further drug development for the treatment and prevention of SARS-CoV-2 infection owing to their good safety, broad-spectrum antiviral activities, and multi-organ protective capacity. Here, we review current knowledge of the characteristics-chemical composition, bioactive properties, and putative mechanisms of action-of natural bioactive dietary flavonoids with the potential for targeting SARS-CoV-2 and its variants. Notably, we present promising strategies (combination therapy, lead optimization, and drug delivery) to overcome the inherent deficiencies of natural dietary flavonoids, such as limited bioavailability and poor stability.

Synergistic Combination of Letrozole and Berberine in Ascorbic Acid-Stabilized AuNPs: A Promising Solution for Breast Cancer.

Breast cancer is a deadly disease that affects countless women worldwide. The most conventional treatments for breast cancer, such as the administration of anticancer medications such as letrozole (LTZ), pose significant barriers due to the non-selective delivery and low bioavailability of cytotoxic drugs leading to serious adverse effects and multidrug resistance (MDR). Addressing these obstacles requires an innovative approach, and we propose a combined strategy that synergistically incorporates LTZ with berberine (BBR) into stabilised AuNPs coated with ascorbic acid (AA), known as LTZ-BBR@AA-AuNPs. The LTZ-BBR@AA-AuNPs, a novel combined drug delivery system, were carefully designed to maximise the entrapment of both LTZ and BBR. The resulting spherical nanoparticles exhibited remarkable efficiency in trapping these two compounds, with rates of 58% and 54%, respectively. In particular, the average hydrodynamic diameter of these nanoparticles was determined to be 81.23 ± 4.0 nm with a PDI value of only 0.286, indicating excellent uniformity between them. Furthermore, their zeta potential was observed to be -14.5 mV, suggesting high stability even under physiological conditions. The release profiles showed that after being incubated for about 24 h at pH levels ranging from acidic (pH = 5) to basic (pH = 7), the percentage released for both drugs ranged from 56-72%. This sustained and controlled drug release can reduce any negative side effects while improving therapeutic efficacy when administered directly to cancer. MDA-MB-231 cells treated with LTZ-BBR@AA-AuNPs for 48 h exhibited IC50 values of 2.04 ± 0.011 μg/mL, indicating potent cytotoxicity against cells. Furthermore, the nanoparticles demonstrated excellent stability throughout the duration of the treatment.

Construction and application of microneedle-mediated photothermal therapy and immunotherapy combined anti-tumor drug delivery system

Conventional treatments for tumors were frequently accompanied by drawbacks and side effects. It might be useful to use the revolutionary microneedle technology which combines photothermal therapy with tumor immunotherapy. In this study, we created a microneedle drug delivery system with mercapto-modified gold nanorods and immune checkpoint blocker anti-PD-1 polypeptide. With good mechanical strength, the microneedle system can efficiently penetrate the skin and deliver drugs. When inserted into human skin, anti-PD-1 peptides and gold nanorods can be released, boosting the capacity of cytotoxic T lymphocytes to destroy tumor cells. Additionally, the elimination of the tumor is aided by the production of heat while being exposed to near-infrared light. This microneedle drug delivery system can enhance the immunological reaction and prolong the survival time of mice. Moreover, it has been demonstrated that the system has mild toxic and side effects on normal tissues and can effectively inhibit the growth of tumors, indicating a bright prospect for the treatment of cancers.