Anticancer Drug Delivery System Research Articles

Green Synthesis of Silver Nanoparticles Using Doxycycline: Evaluation of Antimicrobial Potential and Organ-specific Toxicity

Silver nanoparticles (Ag-NPs) have wide applicability as antimicrobial, biomedical, and anti-cancer drug delivery systems. This study aimed to synthesize Ag-NPs using green methodology to assess their antimicrobial properties and toxicity. Ag-NPs were prepared using doxycycline, an antibiotic serving as a reducing and capping agent. The synthesized Ag-NPs were characterized by ultraviolet-visible spectrophotometry, X-ray diffraction, scanning electron microscopy, and Fourier-transform infrared spectrometry. The antimicrobial efficacy of doxycycline-mediated Ag-NPs was assessed on Candida species in vitro and for toxicity in male albino mice in vivo. The Ag-NPs showed a surface plasmon resonance at 411 nm, indicating a 90 nm average size and spherical shape. Toxicity was tested on mouse organs (liver, kidney, spleen, heart and stomach) using three Ag-NP doses (50, 100, 200 mg/kg) over 14 days. The synthesized Ag-NPs produced large inhibition zones against two well-known fungal species, C. albicans and C. tropicalis, demonstrating their antimicrobial potential. The Ag-NPs showed varying degrees of toxicity in different mouse organs, depending on the administered dose, with more pronounced adverse effects observed at higher concentrations. Periodic administration of Ag-NPs at low-dose volumes holds promise as a safe approach to their use as antimicrobial agents. Low-dose Ag-NPs are minimally toxic and show strong antimicrobial efficacy.

Biosynthesis of pH-Responsive Mesoporous Silica Nanoparticles from Cucumber Peels for Targeting 3D Lung Tumor Spheroids.

Lung adenocarcinoma is considered to be one of the primary causes of cancer-related deaths globally. Conventional treatments, such as chemotherapy and radiation therapy taken together, have not significantly lowered mortality rates. Repositioning of authorized anticancer medications supported by nanotechnology has therefore emerged as an effective strategy to close such gaps. In this context, mesoporous silica nanoparticles (MSNs) were biosynthesized from cucumber peels and were loaded with doxorubicin, a common anticancer drug to form doxorubicin-bound mesoporous silica nanoparticles (DMSNs). The study addresses a sustainable method for turning waste materials into MSNs, which can be used to create multifunctional nanosystems. The therapeutic module (DMSNs) was designed specifically to target 2D monolayer cells and 3D tumor spheroids of lung adenocarcinoma cancer. The DMSNs demonstrated notable antiproliferative activity and effective intracellular localization in addition to being biocompatible and innately fluorescent. Subsequent investigations revealed significant antibacterial activity against Staphylococcal infection, which is primarily prevalent in lung cancer patients. Thus, the developed MSNs held promising potential for anticancer drug delivery systems and have antibacterial potential to treat bacterial infections in patients with lung cancer. Furthermore, the cucumber peel-mediated synthesis of MSNs could also aid in the management of food waste and promote the adoption of the waste-to-health paradigm for sustainable solutions.

Silk fibroin microspheres with photothermal nanocarrier encapsulation for anticancer drug delivery

Controlled drug release systems are pivotal in optimizing therapeutic outcomes and mitigating side effects in treatment protocols. While traditional delivery vectors such as liposomes, micro/nanoparticles, and microspheres are effective, they often struggle with consistency in drug release rates. This study addresses these issues by integrating stimuli-responsive elements specifically magnetic, thermal, and pH-responsive components into drug delivery systems for precise control. Central to our approach is the use of silk fibroin (SF), chosen for its superior biocompatibility and tunable degradation kinetics. We developed uniform carrier microspheres (CMs) by embedding polydopamine nanoparticles (PDA NPs) into SF microspheres using a custom-designed microfluidic platform. The development process and the application of this platform are detailed, highlighting the precision in control achievable. These CMs showcased enhanced photothermal effects, with the thermal response finely adjustable by altering the PDA NPs concentration, achieving a notable temperature increase of 24.5°C at 7.4 wt% concentration. High drug loading capacity (7.5%) and encapsulation efficiency (91.6%) were achieved, along with a pH-responsive release profile under near-infrared irradiation, paving the way for targeted anticancer drug delivery systems using the model drug doxorubicin hydrochloride. These findings underscore the potential of the developed CMs for external topical application, offering promising prospects for targeted cancer therapy utilizing drug-loaded microspheres.

Engineered 1,6-heptadiynes based polymeric prodrug system for anticancer drug delivery

Diacetylene moiety, DIOL was functionalized to chemotherapeutic drug, chlorambucil and water-soluble moiety poly(ethylene glycol) to get our macromonomer MPDC. MPDC was further cyclopolymerized using Hoveyda Grubbs’ second generation catalyst, results to form polymer PMPDC. Amphiphilic nature of PMPDC leads to self-assembly in water which was characterized by dynamic light scattering and transmission electron microscope. Cytotoxicity study was performed with HeLa and MCF 7 cancer cell lines which showed good cell growth inhibition. As PMPDC having non-fluorescent property, another polymer PMPDP was synthesized as control using 1-pyrenebutyric acid which was further used for drug release at different pH and cell internalization study. Increase in internalization of polymer with increase in concentration was observed in both HeLa and MCF 7 cells. Formation of all the compounds were characterized carefully by different analytical techniques.

Preparation of Disulfide/Trisulfide Core-Cross-Linked Polycarbonate Nanocarriers for Intracellular Reduction-Triggered Drug Release.

Polymeric nanocarriers have attracted significant attention in the field of anticancer drug delivery due to their unique advantages. However, designing nanocarriers that can maintain stability in the bloodstream while achieving specific drug release within tumor cells remains a major challenge. To address this issue, constructing reversible cross-linked polymeric nanocarriers that are sensitive to the intracellular reducible glutathione (GSH) characteristic of the tumor microenvironment is a promising strategy. Based on this, we designed and synthesized two novel six-membered bicyclic carbonate monomers containing disulfide (DSBC) and trisulfide (TSBC) bonds. Through a one-step ring-opening polymerization, a series of reduction-sensitive polycarbonate copolymers (i.e., PEG-PDSBC and PEG-PTSBC) were prepared, and doxorubicin (DOX)-loaded nanoparticles were fabricated using a nanoprecipitation method. The in vitro drug release behaviors of these nanoparticles were systematically investigated. The results showed that these polymers, due to the cross-linked structure formed by the ring-opening polymerization of their bicyclic monomers, could self-assemble into stable nanoparticles. Under different concentrations of glutathione, DOX-loaded PEG-PTSBC nanoparticles demonstrated faster drug release, indicating more optimized intracellular drug release properties. Further cytotoxicity experiments revealed that both types of blank nanoparticles exhibited good biocompatibility with the 4T1 and NIH-3T3 cells. Fluorescence microscopy and flow cytometry results further indicated that DOX-loaded PEG-PTSBC nanoparticles released more drugs in 4T1 cells, significantly inhibiting tumor cell growth compared with DOX-loaded PEG-PDSBC nanoparticles, with no noticeable difference in NIH-3T3 normal cells. In conclusion, this study suggests that trisulfide cross-linked polycarbonate-based nanocarriers hold promise as an anticancer drug delivery system that combines stability in the bloodstream with specific intracellular drug release, offering new insights for the development of novel, efficient, and safe anticancer nanomedicines.

Novel Pseudomonas putida-derived nanoliposomes enhance the inhibition of MCF-7 breast cancer cells by superb intracellular uptake of doxorubicin

In this study, we aimed to utilize phospholipids from the bacterium Pseudomonas putida (PP) as a plentiful, safe, and accessible resource for creating nanoliposomes to deliver doxorubicin (Dox) to MCF-7 breast cancer cells. This bacterium provides a cost-effective source of phospholipids commonly used in nanoliposome production, with no toxicity or adverse environmental impact. To this end, molecular dynamics (MD) simulations were first conducted to evaluate the feasibility of this approach and to analyze the behavior and interaction of Dox with the nanoliposomes. The phospholipids of PP were then extracted using Folch's technique. Subsequently, Dox-loaded PP-derived nanoliposomes (PNL-Dox) were developed using the thin-film method. The physicochemical properties of the fabricated nanocarrier were then investigated and the anticancer effects of this system were tested on MCF-7 cells. The results of the MD simulations indicated that Dox reacted with all of the phospholipids through hydrogen bonds without affecting the fluidity, stability, and thickness of the nanoliposome membrane. Additionally, a small number of Dox molecules interacted with the nanocarrier membrane, while the remaining were located in its interior. The physicochemical investigation results showed that PNL-Dox had an average particle size and zeta potential of 271.7 ± 7.1 nm and −8.8 ± 3.3 mV, respectively. Scanning electron microscopy revealed that the particles were spherical and did not show any signs of aggregation. Drug release of PNL-Dox was gradual at pH 7.4 and 6.5, with a significantly higher release at pH 6.5. In vitro studies demonstrated successful uptake of PNL-Dox by MCF-7 cells, resulting in cytotoxicity within 24 and 48 h of treatment. Also, it increased apoptosis and reduced the production of reactive oxygen species (ROS) in these cells. Our study showcased the potential of PP phospholipids to form a promising anti-cancer drug delivery system, opening up new possibilities for the treatment of all types of cancers.

Effect of a supramolecular delivery system based on hyaluronic acid with cyclodextrin on the antitumor properties of oxaliplatin in vitro

One of the modern approaches to the treatment of cancer is the creation of targeted delivery systems for anticancer drugs, which allows increasing the concentration of the delivered substance in the right place and preventing its accumulation in healthy organs and tissues. At the same time, one can also expect an increase in the duration and effectiveness of the drugs, as well as a reduction in side effects during therapy. The hyaluronic acid receptor CD44, which, according to the literature, is highly expressed in many types of tumors and regulates metastasis, is a promising target for targeted delivery of anticancer drugs. The purpose of this study was to evaluate the effect of a supramolecular delivery system based on hyaluronic acid with nanosized cavitand cyclodextrin on the antitumor properties of oxaliplatin in vitro. Cell lines 1301, SK-MEL-28 and B16 were used as tumor cells. Cells were cultured in the presence of a delivery system based on hyaluronic acid (HACD), oxaliplatin (OX), and their complex (HACD-OX) at various concentrations in complete culture medium RPMI-1640 containing 0.3% L-glutamine, 4% gentamicin and 10% inactivated FBS serum for 48 hours in a humidified atmosphere of 5% CO2 at 37°C. The effect of the studied compounds on the viability of cell cultures was assessed using the WST test. It was shown that in the case of the T-cell lymphoma cell line 1301, the HACD delivery system did not affect the ability of OX to reduce the viability of tumor cells of this line; the effect of free oxaliplatin and the complex was comparable. However, in the case of melanoma cells (B16 and SK-MEL-28), the HACD-DOX complex has a more pronounced antitumor effect, causing a statistically significant decrease in the viability of B16 and SK-MEL-28 cells compared to free oxaliplatin.

Triggering multiple modalities of cell death via dual-responsive nanomedicines to address the narrow therapeutic window of β-lapachone

The clinical translation of the anticancer drug β-lapachone (LAP) has been limited by the narrow therapeutic window. Stimuli-responsive anticancer drug delivery systems have gained tremendous attention in recent years to alleviate adverse effects and enhance therapeutic efficacy. Here, we report a dual pH- and enzyme-responsive nanocarrier to address the above issue of LAP. In detail, the epigallocatechin gallate (EGCG) and ferric ions were employed to engineer nanoscale ferric ion-polyphenol complexes where LAP was physically encapsulated therein. The coordination bond between Fe3+ and the catechol moiety of EGCG was sensitive to the low pH, enabling the triggered cargo release in the acidic endosomes/lysosomes. Afterward, the released LAP was activated by the overexpressed NAD(P)H: quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1) in the tumor cells, followed by the generation of reactive oxygen species (ROS), and the induction of oxidative stress and apoptotic cell death. Meanwhile, EGCG could upregulate gasdermin E (GSDME), and ferric ions were involved in the Fenton reaction. Hence, EGCG and ferric ions could sensitize the toxicity of LAP through the induction of multiple cell death pathways (e.g., pyroptosis, ferroptosis, apoptosis, and necroptosis). The current work enlarged the LAP’s therapeutic window via controlled cargo release and vehicle sensitization.

Latest Delivery Advancements of Lipid Nanoparticles for Cancer Treatment.

As one of the primary causes of illness and death globally, cancer demands novel and potent treatment approaches, which is why lipid nanoparticles (LNPs) have gained attention as a promising delivery system for anticancer drugs with precision and efficacy. The article discusses the salient characteristics of LNPs, such as the lipid components, particle size, polydispersity index, and encapsulation efficiency, followed by strategies that enhance their remarkable drug delivery capabilities. The articles explore LNPs ability to improve the solubility, stability, and bioavailability of various chemotherapeutics, nucleic acids, and immunotherapeutic modalities. It also highlights the recent advancement in surface modification of LNPs, which is essential to improve their effectiveness. Tailored coatings of LNPs improve targeting precision, stability, and biocompatibility; enhancing their transport to boost therapeutic efficacy for cancer targeting. The review summarizes the recent advancements made in using LNPs to treat different forms of cancer and focuses on the most recent clinical studies. Overall, the review highlights that the LNPs can target and treat cancer in a tailored manner through gene therapy, RNA interference, and immunotherapy.

Mapping the Nanotechnology Patent Landscape in the Field of Cancer.

Currently, cancer is still a significant disease that seriously endangers human health. Therefore, advanced diagnostic technology and treatment protocols are urgently needed. The rapid development of nanotechnology is expected to provide new ideas for cancer diagnosis and treatment. The research aims to comprehensively demonstrate the hotspots of nanotechnology applications in cancer. In this study, an International Patent Classification codes co-occurrence network is constructed to visualize the technology landscape by simultaneously locating and ranking technologies that play an integral role in nanotechnology diffusion and bridging in the field of cancer. In addition, community identification and topic modeling highlight the latent topics in patent documents. The visualization results of the patent network yield five main clusters: Cluster 0 is a nanoparticle composition delivery system with liposomes as the primary carrier. Cluster 1 is mainly represented by nano-immunotherapy with immune checkpoint inhibitors. Cluster 2 is nano phototherapy based on photodynamic therapy and photothermal therapy. Cluster 3 is diagnostic imaging involving nanotechnology. Cluster 4 is a drug delivery system with nanovesicles and albumin nanoparticles as carriers. It was found that carriers represented by liposomes, vesicles, and albumin nanoparticles are essential nanomaterials in the current anticancer drug delivery systems. Integrating next-generation immunosuppressants and nanotechnology will become an important development direction for future immunotherapy. Organic/inorganic nanomaterials are pivotal in cancer imaging diagnosis and phototherapy.

PBMC-engrafted humanized mice models for evaluating immune-related and anticancer drug delivery systems.

Immune-related drug delivery systems (DDSs) in humanized mouse models are at the forefront of cancer research and serve as bridges between preclinical studies and clinical applications. These systems offer unique platforms for exploring new therapies and understanding their interactions with human cells and the immune system. Here, we focus on a DDS and a peripheral blood mononuclear cell (PBMC)-engrafted humanized mouse model that we recently developed, and consider some of the key components, challenges, and applications to advance these systems towards better cancer treatment on the basis of a better understanding of the immune response. Our DDS is unique and has a dual function, an anticancer effect and a capacity to fine-tune the immune reaction. The PBL-NOG-hIL-4-Tg mouse system is superior to other available humanized mouse systems for the development of such multifunctional DDSs because it supports the rapid reconstruction of an individual donor's immunity and avoids the onset of graft-versus-host disease.

Functionalizing Sgc8-Paclitaxel Conjugates with F-Base Modifications: Targeted Drug Delivery with Optimized Cardiac Safety.

Recent advancements in cancer treatment have improved patient prognoses, but chemotherapy induced cardiotoxicity remains a prevalent concern. This study explores the potential of F-base-modified aptamers for targeted drug delivery, focusing on their impact on cardiotoxicity. From the phosphoramidite, F-base-functionalized Sgc8-F23 was prepared in an automated and programmable way, which was further reacted with paclitaxel (PTX) to give the F-base- modified aptamer Sgc8-paclitaxel conjugates (Sgc8-F23-PTX) efficiently. The conjugate exhibited prolonged circulation time and enhanced efficacy as a precision anticancer drug delivery system. Echocardiographic assessments revealed no exacerbation of cardiac dysfunction after myocardial infarction (MI) and no pathological changes or increased apoptosis in non-infarcted cardiac regions. Autophagy pathway analysis showed no discernible differences in Sgc8-F23-PTX-treated cardiomyocytes compared with controls, in contrast to the increased autophagy with nanoparticle albumin-bound-paclitaxel (Nab-PTX). Similarly, apoptosis analysis showed no significant differences. Moreover, Sgc8-F23-PTX exhibited no inhibitory effect on hERG, hNav1.5, or hCav1.2 channels. These findings suggest the safety and efficacy of F-base-modified Sgc8 aptamers for targeted drug delivery with potential clinical applications. Further research is warranted for clinical translation and exploration of other drug carriers.

Biopolymer-Based Nanomedicine for Cancer Therapy: Opportunities and Challenges.

Cancer, as the foremost challenge among human diseases, has plagued medical professionals for many years. While there have been numerous treatment approaches in clinical practice, they often cause additional harm to patients. The emergence of nanotechnology has brought new directions for cancer treatment, which can deliver anticancer drugs specifically to tumor areas. This article first introduces the application scenarios of nanotherapies and treatment strategies of nanomedicine. Then, the noteworthy characteristics exhibited by biopolymer materials were described, which make biopolymers stand out in polymeric nanomedicine delivery. Next, we focus on summarizing the state-of-art studies of five categories of proteins (Albumin, Gelatin, Silk fibroin, Zein, Ferritin), nine varieties of polysaccharides (Chitosan, Starch, Hyaluronic acid, Dextran, cellulose, Fucoidan, Carrageenan, Lignin, Pectin) and liposomes in the field of anticancer drug delivery. Finally, we also provide a summary of the advantages and limitations of these biopolymers, discuss the prevailing impediments to their application, and discuss in detail the prospective research directions. This review not only helps readers understand the current development status of nano anticancer drug delivery systems based on biopolymers, but also is helpful for readers to understand the properties of various biopolymers and find suitable solutions in this field through comparative reading.

Thermo and pH-responsive nanocarriers based on mesocellular silica foam and poly(N-vinylcaprolactam-co-methacrylic acid): Synthesis, characterization, and in vitro cytotoxicity assay

Smart hybrid nanocarriers were prepared by grafting poly(N-vinylcaprolactam-co-methacrylic acid) (poly(NVCL-co-MAA)) onto mesocellular silica foams (MCF silica) to evaluate them as controlled delivery systems of doxorubicin (DOX). The development of these nanocarriers began with the synthesis of MCF silica with interconnected porous structures and an average pore diameter of 27 nm. Then, free radical polymerization was used to graft the smart copolymer, and some parameters such as comonomer concentration and reaction time were studied. The DOX was loaded by immersion in an aqueous drug solution, while the in vitro release was investigated at different pHs (7.4, 5.8) and temperatures (25, 37 °C). In addition, the cytotoxicity of nanocarriers was investigated in vitro using the direct contact method with human breast cancer cells (SKBR3). In general, hybrid nanocarriers with copolymer graft percentages ranging from 30 to 60 % were obtained. On the other hand, at higher grafting of poly(NVCL-co-MAA) onto MCF silica, higher drug loading (up to 6.41 × 10−2 mg DOX/mg HN) was observed. Furthermore, in vitro DOX release results suggested that the nanocarriers released up to 52 % at 37 °C and a pH of 5.8. Finally, the in vitro cytotoxicity assay revealed that the DOX-loaded hybrid nanocarriers were cytotoxic to SKBR3 cells, indicating a controlled administration of DOX from the nanocarriers compared to free DOX. These results suggest that nanocarriers could have great potential for use as controlled delivery systems of anticancer drugs.

Surface charge accumulation of functionalized carbonized polymer dots selectively induces lysosomal membrane permeabilization of breast cancer cells

Lysosomal membrane permeabilization (LMP) has become an attractive strategy in tumor therapy. However, non-specific cytotoxicity caused by LMP remains a challenge; whether lysosomal-dependent autophagy process affected by lysosomal damage is still unclear. Here, we provide a carbonized polymer dots (CPDs)-based lysosomal targeted nano-strategy that mediates specific cytotoxicity to breast cancer cells by inducing LMP and disruption of autophagy degradation. CPDs functionalized via covalent conjugation with PpIX modified cathepsin D (CTSD) specific substrate peptide (CPDs-PP) were designed to achieve the selectivity to breast cancer cells. The effects and underlying mechanism of CPDs-PP on lysosomal membrane integrity and autophagic flux were determined. CPDs-PP with pH-dependent protonation and CTSD-responsive surface positive charge accumulation property at specific pH were obtained. Conversion of CPDs-PP to CPDs-P and ratiometric green–red fluorescence switching were observed in breast cancer cells with high expression of CTSD. It has been confirmed that CPDs-PP induced LMP and autophagic flux blockage of breast cancer cells. Lysosomal lipid accumulation was demonstrated to be the potential mechanism. CPDs-PP-induced LMP exhibited selective cytotoxicity to adherent tumor cells and tumor spheres, which was furtherly enhanced by spatiotemporal controlled lysosomal specific photodamage. This strategy offers promise for utilization of lysosome-targeting nanocarriers for anti-cancer pro-drugs and drug delivery systems.

Enhanced anti-breast cancer activity of green synthesized selenium nanoparticles by PEGylation: induction of apoptosis and potential anticancer drug delivery system

Breast cancer is a disease associated with high morbidity and mortality rates worldwide. The potential use of biogenic nanoparticles as alternative anticancer agents has been immensely acknowledged in several studies, particularly selenium nanoparticles (SeNPs). Nanoparticles were synthesised using the aqueous extract of Moringa peregrine (MPM-SeNPs) and were PEGylated (PEG-MPM-SeNPs). MPM-SeNPs were characterised by chemical and physical techniques. The successful capping of MPM-SeNPs with PEG was confirmed by spectrophotometric measurements and via Fourier-transform infrared spectroscopy (FT-IR) analysis. Furthermore, the effect of PEGylation of MPM-SeNPs on enhancing their anti-breast cancer activity and as a drug delivery agent was evaluated. Therefore, the loading efficiency and release of DOX at different pH values were measured; the antiproliferative activity of PEG-MPM-SeNPs against the adenocarcinoma breast cancer cell line (MDA-MB-231) was evaluated and compared with that of biogenic MPM-SeNPs and DOX-conjugated PEG-MPM-SeNPs. PEG-MPM-SeNPs and DOX-PEG-MPM-SeNPs had reduced IC50 values compared to MPM-SeNPs; IC50 of 11.54 ± 1.74 and 31.27 ± 2.9 μg mL−1 compared to 71.4 ± 3.4 μg mL−1, respectively. MPM-SeNPs and PEG-MPM-SeNPs caused apoptosis to MDA-MB-231 cells with a significant decrease in the mitochondrial membrane potential (MMP), increase in the released cytochrome C (Cyt C), and activation of caspase-3/9 (P < 0.05). Linking DOX to PEG-MPM-SeNPs led to an increase in caspase-3/8 concentrations and an increase in the released Cyt C, but there were non-significant differences in MMP (P > 0.1) between treated and untreated control cancer cells. MPM-SeNPs and PEG-MPM-SeNPs caused apoptotic reactions via an intrinsic pathway, while linking DOX to PEG-MPM-SeNPs caused apoptosis in cancer cells through an extrinsic pathway.

Self-Immolative Domino Dendrimers as Anticancer-Drug Delivery Systems: A Review.

Worldwide cancer statistics have indicated about 20 million new cancer cases and over 10 million deaths in 2022 (according to data from the International Agency for Research on Cancer). One of the leading cancer treatment strategies is chemotherapy, using innovative drug delivery systems (DDSs). Self-immolative domino dendrimers (SIDendr) for triggered anti-cancer drugs appear to be a promising type of DDSs. The present review provides an up-to-date survey on the contemporary advancements in the field of SIDendr-based anti-cancer drug delivery systems (SIDendr-ac-DDSs) through an exhaustive analysis of the discovery and application of these materials in improving the pharmacological effectiveness of both novel and old drugs. In addition, this article discusses the designing, chemical structure, and targeting techniques, as well as the properties, of several SIDendr-based DDSs. Approaches for this type of targeted DDSs for anti-cancer drug release under a range of stimuli are also explored.

Dual ionotropic crosslinked biopolymer magnetic nanocomposites as 5‐Fluorouracil nanocarrier for potential colorectal cancer treatment

AbstractThis study aimed to synthesize dual‐crosslinked chitosan‐alginate nanocomposites (Cs‐Alg/IO NCs) using green‐synthesized iron oxide nanoparticles (IO, Fe3O4 NPs) for drug delivery application. The NCs, formed via ionotropic gelation with sodium tripolyphosphate (TPP) and calcium chloride (CaCl2) as crosslinking agents for Cs and Alg, respectively, and further characterized for physiochemical properties. The presence of Fe3O4 NPs and 5‐Fluorouracil (5FU) increased hydrodynamic size (153.12 ± 0.57 to 207.64 ± 3.59 nm). Morphological studies revealed NC agglomeration within nanoscales. 5FU‐loaded Cs‐Alg/IO NCs (Cs‐Alg/IO 5FU NCs) exhibited superparamagnetic behavior and sustained drug release under various pH conditions. Cytotoxicity assays on colon cancer cells (HCT116 and HT‐29) and normal colon cells (CCD‐112) indicated higher cancer cell selectivity (selectivity index, SI = 1.91) in 2D models. Elevated IC50 values in 3D models were linked to lower drug loading capacity (LC) and encapsulation efficiency (EE). Overall, the study highlights the potential of dual‐crosslinked biopolymer NCs with green‐synthesized Fe3O4 NPs for developing an anticancer drug delivery system in colorectal cancer treatment.Highlights Synthesis of 5FU‐loaded dual crosslinked Cs‐Alg/IO NCs and Cs‐Alg IPN. Physicochemical characterization of cross‐linked magnetic nanocarriers. Investigation of sustained drug release using superparamagnetic nanocarriers. Evaluation of selective cytotoxicity for Cs‐Alg/IO 5FU NCs.

Zeolitic Imidazolate Frameworks Based Anticancer Drug Delivery System Associated with Dual Action of Surface Charge and Lewis Base Ligand

AbstractZeolitic imidazole frameworks (ZIFs), which combine the favorable characteristics of tunable porosity, controlled structure, and facile functionalization, are explored as a novel class of nanocarriers for biomedical applications. In this study, different ZIF materials are investigated, including ZIF‐8, ZIF‐67, ZIF‐90, ZIF‐92, and ZIF‐108, with the same sodalite topology as the adenosine‐5′‐triphosphate (ATP)‐triggered drug delivery systems. Results indicated that ZIF‐90 and ZIF‐108 displayed good biological compatibility and efficiently accumulated in the mitochondria through competitive coordination between the metal nodes of the ZIFs and ATP, suggesting efficient intracellular delivery. With further interactions between these metal ions and ATP, the encapsulated drugs are released from the ZIF nanoparticles, thereby achieving optimal anti‐tumor activity. Through a systematic evaluation of the physicochemical properties of different ZIFs, it demonstrates that the surface charges of ZIFs have a significant impact on the cytotoxicity of cells, whereas the Lewis basicity of imidazole‐based ligands plays an essential role in the competitive coordination between the metal ions and ATP. These findings provide a potential method for screening ZIFs based nanocarriers with minimal toxicity and explain the different delivery efficiencies of these materials with similar topologies.

Expression of Concern: pH-Responsive Anticancer Drug Delivery Systems: Insights into the Enhanced Adsorption and Release of DOX Drugs using Graphene Oxide as a Nanocarrier

Expression of Concern: pH-Responsive Anticancer Drug Delivery Systems: Insights into the Enhanced Adsorption and Release of DOX Drugs using Graphene Oxide as a Nanocarrier