Deliver Doxorubicin Research Articles

Cell membrane camouflaged Cu-doped mesoporous polydopamine for combined CT/PTT/CDT synergistic treatment of breast cancer

Currently, traditional monotherapy for cancer often results in indiscriminate attacks on the body, leading to the emergence of new health problems. To confront these challenges, multimodal combination therapy has become necessary. However, how to develop new smart nanomaterials through green synthesis methods, delivering drugs while simultaneously synergizing multimodal combination therapies for tumor treatment, remains a topic of great significance. In this study, a biomimetic composite nanomaterial (RM-Cu/P) composed of mesoporous polydopamine (MPDA) as the core and red blood cell membranes (RBCMs) as the shell was synthesized as a drug carrier to deliver doxorubicin (DOX) while achieving synergistic chemotherapy, photothermal and chemodynamic therapy (CT/PTT/CDT). Herein, the nanoparticles were extensively characterized to examine their morphological characteristics, elemental composition, and drug-carrying capacity. Notably, the coating of RBCM reduced the toxicity of the RM-Cu/P@DOX nanoparticles, improved their targeting ability and prolonged their circulation time in vivo. The Cu-doped nanoparticles were capable of initiating a Fenton-like reaction to generate reactive oxygen species (ROS) for CDT, while the photothermal conversion efficiency (η) reached 45.20 % under NIR laser irradiation. Subsequently, the particles were examined by in vivo and in vitro experimental studies in cytotoxicity, cellular uptake, ROS levels, lysosomal escape, and mouse tumor model to evaluate their potential application in antitumor. Compared with monotherapy, the RM-Cu/P@DOX nanoparticles had multiple-stimulation response properties under redox, pH, and NIR, which exhibited the advantage of combined trimodal therapy, resulting in remarkable synergistic antitumor efficacy. In conclusion, this innovative platform exhibited promising applications in smart drug delivery and synergistic treatment of cancer.

Comparative Cellular and In Vivo Anti-cancer studies of Doxorubicin Liposomes Prepared with Different Types of Phospholipids

The selection of lipid components of membrane bilayer determines the rigidity of liposomes affecting drug efficacy, especially for cancer drug delivery. The present study evaluated liposomes with different rigidity for delivering doxorubicin (DOX). In this work, liposomes composed of rigid lipid, hydrogenated soybean phosphatidylcholine (HSPC), were totally or partially substituted with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The liposomes are composed of phosphatidylcholine (HSPC, POPC), with and without combination with DOPE, cholesterol, and DSPE-mPEG2000 with a molar ratio of 57: 38: 5, respectively. Liposomes were prepared using a thin layer hydration method. Then, in vitro cytotoxicity and in vivo antitumor activity of these liposomes were evaluated. Substitution of HSPC with POPC resulted in similar cytotoxicities profiles similar to the DOX solution on C26 colon cancer cells and LLC cells. The DOPE addition to DOX liposomes reduced the antitumor activity. In conclusion, the lipid substitution of HSPC with POPC or DOPE reduced liposome rigidity; however, it lowered the in vivo antitumor activity.

Dynamic Simulations of Interaction of the PEG-DPPE Micelle-Encapsulated Short-Chain Ceramides with the Raft-Included Membrane.

The lipid raft subdomains in cancer cell membranes play a key role in signal transduction, biomolecule recruitment, and drug transmembrane transport. Augmented membrane rigidity due to the formation of a lipid raft is unfavorable for the entry of drugs, a limiting factor in clinical oncology. The short-chain ceramide (CER) has been reported to promote drug entry into membranes and disrupt lipid raft formation, but the underlying mechanism is not well understood. We recently explored the carrier-membrane fusion dynamics of PEG-DPPE micelles in delivering doxorubicin (DOX). Based on the phase-segregated membrane model composed of DPPC/DIPC/CHOL/GM1/PIP2, we aim to explore the dynamic mechanism of the PEG-DPPE micelle-encapsulating DOXs in association with the raft-included cell membrane modulated by C8 acyl tail CERs. The results show that the lipid raft remains integrated and DOX-resistant subjected to free DOXs and the micelle-encapsulating ones. Addition of CERs disorganizes the lipid raft by pushing CHOL aside from DPPC. It subsequently allows for a good permeability for PEG-DPPE micelle-encapsulated DOXs, which penetrate deeper as CER concentration increases. GM1 is significant in guiding drugs' redistributing between bilayer phases, and the anionic PIP2 further helps DOXs attain the inner bilayer surface. These results elaborate on the perturbing effect of CERs on lipid raft stability, which provides a new comprehensive approach for further design of drug delivery systems.

Hierarchical mesoporous silicon and albumin composite microparticles delivering DOX and FU for liver cancer treatment

Drug delivery systems based on hydrogel microcarriers have shown enormous achievements in tumor treatment. Current research direction mainly concentrated on the improvement of the structure and function of the microcarriers to effectively deliver drugs for enhanced cancer treatment with decreased general toxicity. Herein, we put forward novel hierarchical mesoporous silicon nanoparticles (MSNs) and bovine serum albumin (BSA) composite microparticles (MPMSNs@DOX/FU) delivering doxorubicin (DOX) and 5-fluorouracil (FU) for effective tumor therapy with good safety. The DOX and FU could be efficiently loaded in the MSNs, which were further encapsulated into methacrylate BSA (BSAMA) microparticles by applying a microfluidic technique. When transported to the tumor area, DOX and FU will be persistently released from the MPMSNs@DOX/FU and kept locally to lessen general toxicity. Based on these advantages, MPMSNs@DOX/FU could observably kill liver cancer cells in vitro, and evidently suppress the tumor development of liver cancer nude mice model in vivo. These results suggest that such hierarchical hydrogel microparticles are perfect candidates for liver cancer treatment, holding promising expectations for impactful cancer therapy.

Innovative transdermal doxorubicin patches prepared using greenly synthesized iron oxide nanoparticles for breast cancer treatment

ABSTRACT An innovative strategy was formulated to overcome the challenges in delivering doxorubicin (DOX) for breast cancer treatment. Transdermal patches were prepared using carbopol 971 (CP) and polyvinyl alcohol (PVA) loaded with starch-coated iron oxide nanoparticles conjugated to DOX (DOX@St-IONPs). The patches’ physicochemical properties, in vitro drug diffusion, alongside the physical properties of DOX@St-IONPs, and their impact on breast cancer cell lines’ viability were examined. The M1 patch, with a 1:1 CP:PVA ratio and DOX@St-IONPs, showed unique properties, indicating effective delivery. It maintained consistent thickness, weight, and 97% DOX loading. Demonstrated flexibility and acceptable surface pH. M1 displayed fivefold increased drug penetration compared to free DOX patches (flux of 14.85 µg/cm2/h and permeability of 0.95 cm/h), with higher cytotoxicity against triple-negative breast cancer. These results propose promising non-invasive DOX delivery through the developed patches.

Superior doxorubicin cellular delivery effect established by optically active mesoporous silica nanoparticles.

The impact of optically active biomaterials on drug delivery remains a vital and hot topic. To reveal special advantages of optically active mesoporous silica nanoparticles in delivering drug in cells, optically active mesoporous silica nanoparticles deliver doxorubicin (DOX) with chiral behavior in cancer cells was studied. The present work focused on two types of optically active mesoporous silica nanoparticles named as levorotatory optically active mesoporous silica nanoparticles (LOA-MSNs) and dextrorotatory optically active mesoporous silica nanoparticles (DOA-MSNs) and examined their effects on cellular DOX delivery in cancer cells. The obtained LOA-MSNs and DOA-MSNs were regular spheres with particle diameters ranging from 200 to 250nm, and their shell layer was filled with interlaced channels. Our results indicated that LOA-MSNs and DOA-MSNs did not exhibit cytotoxicity towards MCF-7 cells and B16 cells. The cytotoxicity of DOX-loaded LOA-MSNs and DOX-loaded DOA-MSNs were stronger than DOX owing to the synergistic retention and accumulation effect of nanoparticles. More importantly, DOX-loaded DOA-MSNs presented stronger cytotoxicity due to the higher synergistic retention and accumulation effect of DOA-MSNs. These findings suggest that DOA-MSNs with superior cellular delivery of DOX have great potential to advance the development of optical anti-tumor delivery system.

A comparison study between doxorubicin and curcumin co-administration and co-loading in a smart niosomal formulation for MCF-7 breast cancer therapy

Chemotherapy agents often exhibit limited effectiveness due to their fast elimination from the body and non-targeted delivery. Emerging nanomaterials as drug delivery carriers open new expectancy to overcome these limitations in current chemotherapeutic treatments. In this study, we introduce and evaluate a smart pH-responsive niosomal formulation capable of delivering Doxorubicin (DOX) and Curcumin (CUR) in both individually and co-loaded forms. In particular, drug-loaded niosomes were prepared using thin-film hydration method and then characterized via different physicochemical analyses. The pH responsivity of the carrier was assessed by performing a drug release study in three different pH conditions (4, 6.5, and 7.4). Finally, the anticancer efficacy of the therapeutic compounds was evaluated through the MTT assay. Our results showed spherical particles with a size of about 200 nm and -2 mV surface charge. Encapsulation efficiency (EE%) of the nanocarrier was about 77.06 % and 79.08 % for DOX and CUR, respectively. The release study confirmed the pH responsivity of the carrier. The MTT assay results revealed about 39 % and 43 % of cell deaths after treatment with cur-loaded and dox-loaded niosomes, which increased to 74 % and 79 % after co-administration and co-loading forms of drugs, respectively, exhibiting increased anticancer efficacy by selectively delivering DOX and CUR individually or in combination. Overall, these findings suggest that our nanoformulation holds the potential as a targeted and highly effective approach for cancer management and therapy, overcoming the limitations of conventional chemotherapy drugs.

Preparation and characterization of magnetic ferrite-chitosan nanoparticles delivery for DOX

We propose a novel and simple method prepare chitosan (CS) modified magnetic nanoparticles (MNPs) for delivering doxorubicin (DOX), and Mn0.6Zn0.4Gd0.04Fe1.96O4 was chosen as the MNPs. Extensive efforts have been made to create a DOX loaded MNPs/CS composite using acetic acid. The MNPs/CS/DOX nanocomposites analyzed using by Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), Transmission electron microscopy (TEM) and Vibrating sample magnetometer (VSM), firstly. Then the factors such as the weight ratios between CS and MNPs, acetic acid concentration, and DOX concentration were studied for their influence on the loading capacity and encapsulation efficiency of MNPs/CS. Experiment results revealed that DOX was loaded on the MNPs/CS composite successfully. The DOX ratio loaded on MNPs/CS increased with increasing CS and acetic acid concentration. In vitro release tests demonstrated that the MNPs/CS/DOX released quickly in the initial 48 h, and the remaining drug release was more gradual and continuing for 108 h in three solutions (saline, PBS and pH 5.75 solution). Interestingly, 40 % of the release rate of DOX was maintained up to 168 h in PBS solution at 43℃. These results suggest that MNPs/CS/DOX can sustain release over a much longer period, indicating its potential application in magnetic drug carriers.

Metal-organic framework decorated with glycyrrhetinic acid conjugated chitosan as a pH-responsive nanocarrier for targeted drug delivery

Stimulus-responsive nanomaterials have become a hot spot in controllable drug delivery systems researches owing to their spatiotemporal controllable properties based on the differences between tumor microenvironment and normal tissue. Herein, iron (III) carboxylate metal-organic framework nanoparticles coated with glycyrrhetinic acid-chitosan conjugate (MIL-101/GA-CS) were successfully fabricated and acted as the pH-responsive and target-selective system to deliver doxorubicin (DOX) for hepatocellular carcinoma (HCC) therapy. The prepared nanocarrier possess the advantages of uniform size, comparable drug loading efficiency (28.89%), and superior pH-dependent controlled drug release (DOX release of 2.74% and 89.18% within 72 h at pH 7.4 and 5.5, respectively). In vitro cytotoxicity assays showed that the drug-loaded nanocarriers exhibited excellent inhibitory effects on HepG2 cells due to the sustained release of DOX, while the nanocarriers showed no significant toxicity. Furthermore, cell uptake experiments demonstrated that MIL-101-DOX/GA-CS could target HepG2 cells based on receptor-dependent internalization of glycyrrhetinic acid receptors mediated. In vitro 3D hepatoma cell microspheres experiments showed that MIL-101-DOX/GA-CS had excellent penetration and tumor killing ability. Therefore, MIL-101-DOX/GA-CS nanoparticles have a prospective application in cancer therapy as a pH-responsive controlled drug delivery system.

Preoperative administration of a biomimetic platelet nanodrug enhances postoperative drug delivery by bypassing thrombus

The postoperative thrombus attached to the damaged blood vessels severely obstructs drugs from crossing the damaged blood–brain barrier (BBB) and targeting residual glioma cells around surgical margins, leading to glioblastoma (GBM) recurrence. A thrombus-bypassing, BBB-crossing, and surgical margin-targeted nanodrug is needed to address this phenomenon. Encouraged by the intrinsic damaged vascular endothelium chemotaxis of platelets, a platelet membrane-coated nanodrug (PM-HDOX) delivering doxorubicin (DOX) for postoperative GBM treatment is proposed and systematically investigated. Because surgery damages the vascular endothelium on the BBB around the surgical margin, the platelet membrane coating endows PM-HDOX with its inherent capacity to cross the broken BBB and target the surgical margin. Moreover, preoperative administration combined with fast-targeted PM-HDOX can realize the potential of bypassing thrombus. In GBM resection models, PM-HDOX with preoperative administration demonstrated significantly enhanced BBB-crossing and surgical margin-targeted efficacy. In particular, the PM-HDOX intensities around the surgical margins of the preoperative administration group were more than twice that of the postoperative administration group due to bypassing the thrombus formed in the broken BBB. In the antitumor experiment, the preoperative administration of PM-HDOX significantly inhibited the growth of postoperative residual tumors and prolonged the median survival time of mice. In conclusion, preoperative administration of a biomimetic platelet nanodrug can be an efficient and promising drug delivery strategy for residual GBM after surgery.

Mechano-boosting nanomedicine antitumour efficacy by blocking the reticuloendothelial system with stiff nanogels

Nanomedicine has been developed for cancer therapy over several decades, while rapid clearance from blood circulation by reticuloendothelial system (RES) severely limits nanomedicine antitumour efficacy. We design a series of nanogels with distinctive stiffness and investigate how nanogel mechanical properties could be leveraged to overcome RES. Stiff nanogels are injected preferentially to abrogate uptake capacity of macrophages and temporarily block RES, relying on inhibition of clathrin and prolonged liver retention. Afterwards, soft nanogels deliver doxorubicin (DOX) with excellent efficiency, reflected in high tumour accumulation, deep tumour penetration and outstanding antitumour efficacy. In this work, we combine the advantage of stiff nanogels in RES-blockade with the superiority of soft nanogels in drug delivery leads to the optimum tumour inhibition effect, which is defined as mechano-boosting antitumour strategy. Clinical implications of stiffness-dependent RES-blockade are also confirmed by promoting antitumour efficacy of commercialized nanomedicines, such as Doxil and Abraxane.

Mesoporous polydopamine delivery system for intelligent drug release and photothermal-enhanced chemodynamic therapy using MnO2 as gatekeeper.

The non-specific leakage of drugs from nanocarriers seriously weakened the safety and efficacy of chemotherapy, and it was very critical of constructing tumor microenvironment (TME)-responsive delivery nanocarriers, achieving the modulation release of drugs. Herein, using manganese dioxide (MnO2) as gatekeeper, an intelligent nanoplatform based on mesoporous polydopamine (MPDA) was developed to deliver doxorubicin (DOX), by which the DOX release was precisely controlled, and simultaneously the photothermal therapy (PTT) and chemodynamic therapy (CDT) were realized. In normal physiological environment, the stable MnO2 shell effectively avoided the leakage of DOX. However, in TME, the overexpressed glutathione (GSH) degraded MnO2 shell, which caused the DOX release. Moreover, the photothermal effect of MPDA and the Fenton-like reaction of the generated Mn2+ further accelerated the cell death. Thus, the developed MPDA-DOX@MnO2 nanoplatform can intelligently modulate the release of DOX, and the combined CDT/PTT/chemotherapy possessed high-safety and high-efficacy against tumors.

Delivery mechanism of doxorubicin by PEG-DPPE micelles on membrane invasion by dynamic simulations.

Exploiting micelles of polyethylene glycol-dipalmitoylglycerophosphoethanolamine (PEG-DPPE) as a drug delivery approach is of great promise for improving therapeutic targeting and the half-lives of drugs. To optimize the micelle carriers, pending issues concerning the kinetics underlying the carrier-membrane interplay and the specific contributions of the micelle hydrophobic/hydrophilic components remain to be addressed. Relying on MARTINI coarse-grain (CG) molecular dynamics simulations, we explored the carrier-membrane fusion dynamics of PEG-DPPE micelles with different PEG repetitions in delivering doxorubicin (DOX). A bilayer model composed of 20% phosphatidylglycerol (POPG) and 80% phosphatidylcholine (POPC) was constructed to mimic anionic cancer cell membranes. The CG model of DOX was pioneeringly constructed herein, and it was found to distribute at the hydrophilic/hydrophobic interface of the PEGylated micelles, in agreement with experimental results. The free DOXs cause insignificant disorder of the membrane organization, whereas the PEG-DPPE micelles encapsulating DOX lead to a remarkable membrane invasion supported by the order parameter of the lipid acyl carbon tails and the membrane permeation free energy of DOX. The carrier-bilayer interaction shows a stepwise form attributed to the rearrangement of the zwitterionic/anionic lipids upon the absorption of the DOX-micelle complex on a membrane locality, which initiates the rapid release of DOX to the bilayer interior. Benefiting from the enhanced micelle-membrane interplay, the PEG1250-DPPE micelles result in severe bilayer breakage and deeper membrane insertion of DOX compared to the PEG2000-DPPE micelles. This study provides new theoretical insights into the mechanism of PEG-DPPE micelles in delivering drugs through membranes, which is of benefit for further optimization of PEGylated delivery systems.

Redox-sensitive hyaluronic acid-ferrocene micelles delivering doxorubicin for enhanced tumor treatment by synergistic chemo/chemodynamic therepay

In order to solve the defects of chemotherapeutics, numerous collaborative therapy systems have been developed according to the characteristics of tumor microenvironment. Herein, a targeting redox-sensitive micellar system (DOX/FCH) composed of ferrocene (Fc) and hyaluronic acid (HA) was prepared to deliver doxorubicin (DOX) for synergetic chemotherapy and chemodynamic therapy (CDT). DOX/FCH could accurately target the tumor site through high affinity between HA and high-expressed CD44 receptors in human cervical carcinoma (HeLa) cells. The appropriate particle size made it easier for cells to take up the micelles. The DOX released from DOX/FCH reached about 50% in 2 h, because the disulfide bonds were depolymerized in reducing environment which simulate the tumor intracellular environment. Moreover, the production of hydroxyl radical (·OH) was detected both extracellular and intracellular, which indicated that FCH could exert the CDT effect through Fenton reaction to enhance the chemotherapy of DOX. The good biocompatibility in 3T3 cells as well as the obvious cytotoxicity in HeLa cells demonstrated that FCH had the possibility of becoming an excellent nanocarrier. Also, the cytotoxicity of DOX/FCH also confirmed the synergetic effect of CDT of FCH and chemotherapy of DOX. Therefore, DOX/FCH shows great potential in the application of improving the efficacy of combined chemotherapy and CDT.

Biomimetic Targeted Theranostic Nanoparticles for Breast Cancer Treatment.

The development of biomimetic drug delivery systems for biomedical applications has attracted significant research attention. As the use of cell membrane as a surface coating has shown to be a promising platform for several disease treatments. Cell-membrane-coated nanoparticles exhibit enhanced immunocompatibility and prolonged circulation time. Herein, human red blood cell (RBC) membrane-cloaked nanoparticles with enhanced targeting functionality were designed as a targeted nanotheranostic against cancer. Naturally, derived human RBC membrane modified with targeting ligands coated onto polymeric nanoparticle cores containing both chemotherapy and imaging agent. Using epithelial cell adhesion molecule (EpCAM)-positive MCF-7 breast cancer cells as a disease model, the nature-inspired targeted theranostic human red blood cell membrane-coated polymeric nanoparticles (TT-RBC-NPs) platform was capable of not only specifically binding to targeted cancer cells, effectively delivering doxorubicin (DOX), but also visualizing the targeted cancer cells. The TT-RBC-NPs achieved an extended-release profile, with the majority of the drug release occurring within 5 days. The TT-RBC-NPs enabled enhanced cytotoxic efficacy against EpCAM positive MCF-7 breast cancer over the non-targeted NPs. Additionally, fluorescence images of the targeted cancer cells incubated with the TT-RBC-NPs visually indicated the increased cellular uptake of TT-RBC-NPs inside the breast cancer cells. Taken together, this TT-RBC-NP platform sets the foundation for the next-generation stealth theranostic platforms for systemic cargo delivery for treatment and diagnostic of cancer.

Preparation and Evaluation of the Cytoprotective Activity of Micelles with DSPE-PEG-C60 as a Carrier Against Doxorubicin-Induced Cytotoxicity.

To deliver doxorubicin (DOX) with enhanced efficacy and safety in vivo, fullerenol-modified micelles were prepared with the amphiphilic polymer DSPE-PEG-C60 as a carrier, which was synthesized by linking C60(OH)22 with DSPE-PEG-NH2. Studies of its particle size, PDI, zeta potential, and encapsulation efficiency were performed. DOX was successfully loaded into the micelles, exhibiting a suitable particle size [97 nm, 211 nm, 260 nm, vector: DOX = 5:1, 10:1; 15:1 (W/W)], a negative zeta potential of around −30 mv, and an acceptable encapsulation efficiency [86.1, 95.4, 97.5%, vector: DOX = 5:1, 10:1; 15:1 (W/W)]. The release behaviors of DOX from DSPE-PEG-C60 micelles were consistent with the DSPE-PEG micelles, and it showed sustained release. There was lower cytotoxicity of DSPE-PEG-C60 micelles on normal cell lines (L02, H9c2, GES-1) than free DOX and DSPE-PEG micelles. We explored the protective role of DSPE-PEG-C60 on doxorubicin-induced cardiomyocyte damage in H9c2 cells, which were evaluated with a reactive oxygen species (ROS) assay kit, JC-1, and an FITC annexin V apoptosis detection kit for cellular oxidative stress, mitochondrial membrane potential, and apoptosis. The results showed that H9c2 cells exposed to DSPE-PEG-C60 micelles displayed decreased intracellular ROS, an increased ratio of red fluorescence (JC-1 aggregates) to green fluorescence (JC-1 monomers), and a lower apoptotic ratio than the control and DSPE-PEG micelle cells. In conclusion, the prepared DOX-loaded DSPE-PEG-C60 micelles have great promise for safe, effective tumor therapy.

Entrapment and Delivery of Doxorubicin: Employing a Permeable Lipopeptide-Based Hydrogel as an Efficient Cationic Binder.

Lipopeptides have been the subject of great interest as vehicles for drug delivery, but the potential usage of their biological composites has not been extensively studied. Here, the extracellular lipopeptide composite (ELC) of a lipopeptide-producing bacterium was extracted and examined to deliver doxorubicin (DOX) as a cationic drug. MALDI-TOF mass spectrometry analysis on the lipopeptide moiety of ELC revealed that this hydrogel consists of 13 lipopeptide isomers. Furthermore, scanning electron microscope (SEM) studies showed that the permeability of ELC in acidic pH was significantly more than basic condition. In this study, 81% of DOX was successfully entrapped in ELC and the release of the drug was measured in acidic, neutral, and basic conditions. The results indicated that the release profile of the drug in acidic pH was about 10 and 16 fold more than neutral and basic conditions, respectively. Besides, the toxicity of DOX-conjugated ELC against PBMC cells was more than free DOX, suggesting the adequate drug release from ELC. Since the surrounding environment of tumor cells is often acidic, this pH-sensitive carrier could be a candidate for cancer therapy to improve the exposure of tumor cells to the drugs.

Tumor site-specific PEG detachment and active tumor homing of therapeutic PEGylated chitosan/folate-decorated polydopamine nanoparticles to augment antitumor efficacy of photothermal/chemo combination therapy

To effectively promote tumor-targeted delivery of photothermal/chemo combined therapy for boosted antitumor efficacy, the versatile photothermal hybrid polymeric nanoparticles capable of detaching poly(ethylene glycol) (PEG) segments and exposing tumor-targeting folate (FA) moieties in response to tumor extracellular acidity (pHe) are developed to selectively deliver doxorubicin (DOX), a chemotherapy drug, to the tumor sites. Through one-pot co-deposition of dopamine molecules with acidity-responsive benzoic imine-containing PEGylated chitosan (BI-PC) adducts, the hybrid BI-PC/polydopamine (PDA) nanoparticles were attained as DOX vehicles and characterized to have a spherical structure composed of a PDA core surrounded by hydrophilic BI-PC shells. The DOX@BI-PC/PDA nanoparticles not only showed prominent colloidal stability in serum-containing environment and photothermal conversion efficiency, but also exhibited acidity/photothermal-activated drug release. The PEG detachment and FA exposure of FA-DOX@BI-PC/PDA nanoparticles in weak acidic environment appreciably promoted their uptake by FA receptor-overexpressed CT-26 colon cancer cells, thus largely augmenting anticancer potency based on the photothermal/chemo therapy. Importantly, the pHe-responsive FA-DOX@BI-PC/PDA nanoparticles markedly accumulated in CT-26 tumor sites in vivo and inhibited tumor growth without significant systemic toxicity upon the near infrared (NIR)-triggered hyperthermia integrated with DOX chemotherapy. This work presents a practical strategy for improved antitumor potency of photothermal/chemo combination therapy.

Glutathione-Responsive Biodegradable Core–Shell Nanoparticles That Self-Generate H2O2 and Deliver Doxorubicin for Chemo–Chemodynamic Therapy

Glutathione-Responsive Biodegradable Core–Shell Nanoparticles That Self-Generate H₂O₂ and Deliver Doxorubicin for Chemo–Chemodynamic Therapy

Bifunctional folic-conjugated aspartic-modified Fe3O4 nanocarriers for efficient targeted anticancer drug delivery.

Functionalization of nanocarriers has been considered the most promising way of ensuring an accurate and targeted drug delivery system. This study reports the synthesis of bifunctional folic-conjugated aspartic-modified Fe3O4 nanocarriers with an excellent ability to deliver doxorubicin (DOX), an anticancer drug, into the intercellular matrix. Here, the presence of amine and carboxylate groups enables aspartic acid (AA) to be used as an efficient anchoring molecule for the conjugation of folic acid (FA) (EDC–NHS coupling) and DOX (electrostatic interaction). Based on the results, surface functionalization showed little effect on the physicochemical properties of the nanoparticles but significantly influenced both the loading and release efficiency of DOX. This is primarily caused by the steric hindrance effect due to large and bulky FA molecules. Furthermore, in vitro MTT assay of B16–F1 cell lines revealed that FA conjugation was responsible for a significant increase in the cytotoxicity of DOX-loaded nanocarriers, which was also found to be proportional to AA concentration. This high cytotoxicity resulted from an efficient cellular uptake induced by the over-expressed folate receptors and fast pH triggered DOX release inside the target cell. Here, the lowest IC50 value of DOX-loaded nanocarriers was achieved at 2.814 ± 0.449 μg mL−1. Besides, further investigation also showed that the drug-loaded nanocarriers exhibited less or no toxicity against normal cells.