Antitumor Drug Delivery System Research Articles

Construction of anticancer drug incorporated aptamer-functionalized cationic β-lactoglobulin: induction of cell cycle arrest and apoptosis in colorectal cancer

Nanoscale drug delivery systems that are both multifunctional and targeted have been developed using proteins as a basis, thanks to their attractive biomacromolecule properties. A novel nanocarrier, aptamer (AS1411)-conjugated β-lactoglobulin/poly-l-lysine (BLG/Ap/PL) nanoparticles, was developed in this study. To this unique formulation, the as-prepared nanocarrier blends the distinctive features of an aptamer as a chemotherapeutic targeting agent with those of protein nanocarriers. By loading cabazitaxel (CTX) onto the nanocarriers, the therapeutic potential of BLG/Ap/PL could be demonstrated. The CTX-loaded BLG/Ap/PL (CTX@BLG/Ap/PL) showed a regulated drug release profile in an acidic milieu, which could improve therapeutic efficacy in cancer cells and have a high drug encapsulation efficacy of up to 93%. However, compared to free CTX, CTX@BLG/Ap/PL killed colorectal HCT116 cancer cells with a higher efficacy at 24 and 48 h. Further investigation confirms the apoptosis by acridine orange and ethidium bromide (AO/EB), and DAPI staining confirms the morphological changes, chromatin condensation, and membrane blebbing in the treated cell through flow cytometry displayed the release of higher percentages of apoptosis. Cell cycle analysis revealed that CTX@BLG/Ap/PL induced sub-G1 and G2/M phase (apoptosis) at 24 and 48 h. Annexin V/propidium iodide (PI) flow cytometry analysis confirmed that CTX@BLG/Ap/PL induces apoptosis in HCT116 cells. Overall, this study proved that CTX@BLG/Ap/PL had several advantages over free chemotherapeutic drugs and showed promise as a solution to the clinical problems associated with targeted antitumor drug delivery systems.

Evaluation of 3-O-β-D-galactosylated resveratrol-loaded polydopamine nanoparticles for hepatocellular carcinoma treatment

In our previous studies, 3-O-β-D-galactosylated resveratrol (Gal-Res) was synthesized by structural modification and then 3-O-β-D-galactosylated resveratrol polydopamine nanoparticles (Gal-Res NPs) were successfully prepared to improve the bioavailability and liver distribution of Res. However, the pharmacodynamic efficacy and specific mechanism of Gal-Res NPs on hepatocellular carcinoma remain unclear. Herein, liver cancer model mice were successfully constructed by xenograft tumor modeling. Gal-Res NPs (34.2 mg/kg) significantly inhibited tumor growth of the liver cancer model mice with no significant effect on their body weight and no obvious toxic effect on major organs. Additionally, in vitro cellular uptake assay showed that Gal-Res NPs (37.5 μmol/L) increased the uptake of Gal-Res by Hepatocellular carcinoma (HepG2) cells, and significantly inhibited the cell migration and invasion. The experimental results of Hoechst 33342/propyl iodide (PI) double staining and flow cytometry both revealed that Gal-Res NPs could remarkably promote cell apoptosis. Moreover, the Western blot results revealed that Gal-Res NPs significantly regulated the Bcl-2/Bax and AKT/GSK3β/β-catenin signaling pathways. Taken together, the in vitro/in vivo results demonstrated that Gal-Res NPs significantly improved the antitumor efficiency of Gal-Res, which is a potential antitumor drug delivery system.

Biohybrid hydrogel inhibiting β-klotho/HDAC3 axis for hepatocellular carcinoma treatment

Hepatocellular carcinoma (HCC), ranking as the fourth most prevalent cancer globally, has garnered significant attention due to its high invasiveness and mortality rates. However, drug therapies face challenges of inadequate efficacy and unclear mechanisms. Here, we propose a novel biohybrid hydrogel that targets β-klotho (KLB) for HCC treatment. As a dual-network hydrogel, this gel combines gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA) to ensure biocompatibility while enhancing controlled drug release. Notably, it exhibits good storage stability, high drug load capacity, and efficient water absorption. By introducing the HDAC3 inhibitor RGFP966, we can selectively inhibit the activation of KLB. This deactivation effectively blocks the FGF21-KLB signaling pathway and inhibits the progression of HCC. Importantly, we have successfully validated this unique phenomenon both in vivo and in vitro, providing substantial evidence for the efficacy of this hydrogel-based anti-tumor drug delivery system as a promising strategy for HCC treatment. This innovative research outcome brings new hope to the field of tumor therapy, providing a reliable theoretical foundation for future clinical applications.

Research Progress of Disulfide Bond Based Tumor Microenvironment Targeted Drug Delivery System.

Cancer poses a significant threat to human life and health. Chemotherapy is currently one of the effective cancer treatments, but many chemotherapy drugs have cell toxicity, low solubility, poor stability, a narrow therapeutic window, and unfavorable pharmacokinetic properties. To solve the above problems, target drug delivery to tumor cells, and reduce the side effects of drugs, an anti-tumor drug delivery system based on tumor microenvironment has become a focus of research in recent years. The construction of a reduction-sensitive nanomedicine delivery system based on disulfide bonds has attracted much attention. Disulfide bonds have good reductive responsiveness and can effectively target the high glutathione (GSH) levels in the tumor environment, enabling precise drug delivery. To further enhance targeting and accelerate drug release, disulfide bonds are often combined with pH-responsive nanocarriers and highly expressed ligands in tumor cells to construct drug delivery systems. Disulfide bonds can connect drug molecules and polymer molecules in the drug delivery system, as well as between different drug molecules and carrier molecules. This article summarized the drug delivery systems (DDS) that researchers have constructed in recent years based on disulfide bond drug delivery systems targeting the tumor microenvironment, disulfide bond cleavage-triggering conditions, various drug loading strategies, and carrier design. In this review, we also discuss the controlled release mechanisms and effects of these DDS and further discuss the clinical applicability of delivery systems based on disulfide bonds and the challenges faced in clinical translation.

Acyltransferase zinc finger DHHC-type containing 2 aggravates gastric carcinoma growth by targeting Nrf2 signaling: A mechanism-based multicombination bionic nano-drug therapy

The significant regulatory role of palmitoylation modification in cancer-related targets has been demonstrated previously. However, the biological functions of Nrf2 in stomach cancer and whether the presence of Nrf2 palmitoylation affects gastric cancer (GC) progression and its treatment have not been reported. Several public datasets were used to look into the possible link between the amount of palmitoylated Nrf2 and the progression and its outcome of GC in patients. The palmitoylated Nrf2 levels in tumoral and peritumoral tissues from GC patients were also evaluated. Both loss-of-function and gain-of-function via transgenic experiments were performed to study the effects of palmitoylated Nrf2 on carcinogenesis and the pharmacological function of 2-bromopalmitate (2-BP) on the suppression of GC progression in vitro and in vitro. We discovered that Nrf2 was palmitoylated in the cytoplasmic domain, and this lipid posttranslational modification causes Nrf2 stabilization by inhibiting ubiquitination, delaying Nrf2 destruction via the proteasome and boosting nuclear translocation. Importantly, we also identify palmitoyltransferase zinc finger DHHC-type palmitoyltransferase 2 (DHHC2) as the primary acetyltransferase required for the palmitoylated Nrf2 and indicate that the suppression of Nrf2 palmitoylation via 2-bromopalmitate (2-BP), or the knockdown of DHHC2, promotes anti-cancer immunity in vitro and in mice model-bearing xenografts. Of note, based on the antineoplastic mechanism of 2-BP, a novel anti-tumor drug delivery system ground 2-BP and oxaliplatin (OXA) dual-loading gold nanorods (GNRs) with tumor cell membrane coating biomimetic nanoparticles (CM@GNRs-BO) was established. In situ photothermal therapy is done using near-infrared (NIR) laser irradiation to help release high-temperature-triggered drugs from the CM@GNRs-BO reservoir when needed. This is done to achieve photothermal/chemical synergistic therapy. Our findings show the influence and linkage of palmitoylated Nrf2 with tumoral and peritumoral tissues in GC patients, the underlying mechanism of palmitoylated Nrf2 in GC progression, and novel possible techniques for addressing Nrf2-associated immune evasion in cancer growth. Furthermore, the bionic nanomedicine developed by us has the characteristics of dual drugs delivery, homologous tumor targeting, and photothermal and chemical synergistic therapy, and is expected to become a potential platform for cancer treatment.

Spatiotemporally controlled AuNPs@ZIF-8 based nanocarriers for synergistic photothermal/chemodynamic therapy

High efficiency and spatio-temporal control remains a challenge for multi-modal synergistic cancer therapy. Herein, based on gold nanoparticles (AuNPs) and zeolite-like imidazole skeleton material (ZIF-8), a spatio-temporal controllable photothermal/ chemical dynamic/ chemotherapy three modal synergistic anti-tumor nano-carrier (HAZD) was developed. HAZD has a size of 128.75 ± 11.86 nm, a drug loading ratio of 21.5 ± 2.2 % and an encapsulation efficiency of 71.8 ± 1.7 %. Stability, acid responsive release character, outstanding catalytic ability to generate ROS, relatively high thermal conversion efficiency up to 62.38 % and spatio-temporal controllable abilities are also found within this nano-carrier. Furthermore, HAZD performed good antitumor ability in vivo with the comprehensive effects of photothermal/ chemical dynamic/ chemotherapy. The tumor growth inhibition value is 97.1 % within 12 days, indicating its great potential in multi-modal synergistic cancer therapy. Statement of significanceCancer remains one of the major culprits that seriously harm human health currently. With the development of materials and nanotechnology, great improvements have been made in multimodal anti-tumor strategies. However, temporal- and spatial-controllable multi-modal synergistic nanocarriers are urgently awaited for efficient and low-toxicity tumor therapy. This article proposes a spatio-temporally controllable three-modal anti-tumor strategy and designs an anti-tumor drug delivery system based on gold nanoparticles (AuNPs) and zeolite-like imidazole skeleton material (ZIF-8), which shows acid-responsive release characteristics, catalytic ability to generate ROS, relatively high thermal conversion efficiency up to 62.38 %, as well as spatio-temporal controllable abilities. Moreover, it demonstrates outstanding anti-tumor ability, with a tumor growth inhibition value of 97.1 % within 12 days, revealing its significant potential for future personalized and precise anti-tumor treatments.

Development and evaluation of redox-responsive alginate–SS–ibuprofen derivative based anti-tumor target drug delivery system for the controlled release of doxorubicin

Nowadays, self-assembled polymeric micelles from amphiphilic polymer conjugates are urgently needed to enhance drug targeting and release efficiency. On account of the excellent properties of alginate and the redox-responsiveness of disulfide bonds, a redox-sensitive alginate–SS–ibuprofen derivative (LSA–SS–IBU) based anti-tumor target drug delivery system was created by attaching the hydrophobic ibuprofen (IBU) onto the hydrophilic alginate molecular skeleton through disulfide linkages for glutathione (GSH) triggered delivery of doxorubicin hydrochloride (DOX). The structure and self-assembly behavior of the synthesized LSA–SS–IBU was systematically evaluated by FT-IR spectrometer, 1H NMR spectrometer, fluorescence spectrophotometer (FM), transmission electron microscope (TEM) and dynamic light scattering (DLS). Furthermore, the in vitro release of drugs from the LSA–SS–IBU micelles loaded with DOX was examined, along with the assessment of their cytotoxicity to HeLa cells. The resultant LSA–SS–IBU had a critical micelle concentration (CMC) value of 0.19 mg/mL that was able to self-assemble into the spherical micelles with the particle size and zeta potential of 148.2 ± 4.3 nm (PDI = 0.25) and −47.2 ± 0.4 mV, respectively. At a mass ratio of 3:10 for DOX/LSA–SS–IBU, the LSA–SS–IBU micelles achieved drug loading ratio (DLR) and encapsulation efficiency (EE) values of 12.2 % and 46.3 %, respectively. Furthermore, the in vitro drug release study indicated that the total drug release percentage of the drug-encapsulated LSA–SS–IBU micelles in PBS with the presence of 10 mmol/L GSH for 12 h exceeded 67.0 %, demonstrating a substantial increase compared to that in GSH-free PBS. The in vitro cytotoxicity findings indicated that LSA–SS–IBU had good biocompatibility, while the IC50 value and the cell viability of DOX-loaded LSA–SS–IBU micelles cultured with HeLa cells for 48 h was 2.2 μg/mL and less than 20.1 %, respectively, which could significantly inhibit the growth of HeLa cells. Therefore, redox-responsive LSA–SS–IBU micelles had potential applications in cancer therapy for hydrophobic anti-tumor drug delivery.

Brain Delivery of Cisplatin Using Microbubbles in Combination with Ultrasound as an Effective Therapy for Glioblastoma.

Glioblastoma is a highly invasive and fatal disease. Temozolomide, a blood-brain barrier (BBB)-penetrant therapeutic agent currently used for glioblastoma, does not exhibit sufficient therapeutic effect. Cisplatin (CDDP), a versatile anticancer drug, is not considered a therapeutic option for glioblastoma due to its low BBB permeability. We previously investigated the utility of microbubbles (MBs) in combination with ultrasound (US) in promoting BBB permeability and reported the efficacy of drug delivery to the brain using a minimally invasive approach. This study aimed to evaluate the feasibility of CDDP delivery to the brain using the combination of MBs and US for the treatment of glioblastoma. We used mice that were implanted with glioma-261 GFP-Luc cells expressing luciferase as the glioblastoma model. In this model, after tumor inoculation, the BBB opening was induced using MBs and US, and CDDP was simultaneously administered. We found that the CDDP concentrations were higher at the glioblastoma site where the US was applied, although CDDP normally cannot pass through the BBB. Furthermore, the survival was longer in mice treated with CDDP delivered via MBs and US than in those treated with CDDP alone or those that were left untreated. These results suggest that the combination of MBs and US is an effective antitumor drug delivery system based on BBB opening in glioblastoma therapy.

Membrane-Active Mitochondria-Targeted Antitumor Agents and Drug Delivery Systems

Membrane-Active Mitochondria-Targeted Antitumor Agents and Drug Delivery Systems

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.

Advances and Prospects of Prolamine Corn Protein Zein as Promising Multifunctional Drug Delivery System for Cancer Treatment.

Zein is a type of prolamine protein that is derived from corn, and it has been recognized by the US FDA as one of the safest biological materials available. Zein possesses valuable characteristics that have made it a popular choice for the preparation of drug carriers, which can be administered through various routes to improve the therapeutic effect of antitumor drugs. Additionally, zein contains free hydroxyl and amino groups that offer numerous modification sites, enabling it to be hybridized with other materials to create functionalized drug delivery systems. However, despite its potential, the clinical translation of drug-loaded zein-based carriers remains challenging due to insufficient basic research and relatively strong hydrophobicity. In this paper, we aim to systematically introduce the main interactions between loaded drugs and zein, administration routes, and the functionalization of zein-based antitumor drug delivery systems, in order to demonstrate its development potential and promote their further application. We also provide perspectives and future directions for this promising area of research.

Synthesis, characterization, and in vitro anti-tumor activity studies of the hyaluronic acid-mangiferin-methotrexate nanodrug targeted delivery system

In this study, to increase the accumulation of MTX in the tumor site and reduce the toxicity to normal tissues by MA, a novel nano-drug delivery system comprised of hyaluronic acid (HA)-mangiferin (MA)-methotrexate (MTX) (HA-MA-MTX) was developed by a self-assembly strategy. The advantage of the nano-drug delivery system is that MTX can be used as a tumor-targeting ligand of the folate receptor (FA), HA can be used as another tumor-targeting ligand of the CD44 receptor, and MA serves as an anti-inflammatory agent. 1HNMR and FT-IR results confirmed that HA, MA, and MTX were well coupled together by the ester bond. DLS and AFM images revealed that the size of HA-MA-MTX nanoparticles was about ~138 nm. In vitro cell experiments proved that HA-MA-MTX nanoparticles have a positive effect on inhibiting K7 cancer cells while having relatively lower toxicity to normal MC3T3-E1 cells than MTX does. All these results indicated that the prepared HA-MA-MTX nanoparticles can be selectively ingested by K7 tumor cells through FA and CD44 receptor-mediated endocytosis, thus inhibiting the growth of tumor tissues and reducing the nonspecific uptake toxicity caused by chemotherapy. Therefore, these self-assembled HA-MA-MTX NPs could be a potential anti-tumor drug delivery system.

A doxorubicin and siRNA coloaded nanolamellar hydroxyapatite/PLGA electrospun scaffold as a safe antitumor drug delivery system

To circumvent the severe cytotoxicity and drug resistance of chemotherapeutics in cancer chemotherapy, we rationally designed an electrospun nanofibrous delivery system for the codelivery of the doxorubicin (DOX) and small interfering ribonucleic acid (siRNA) to improve antitumor activity and mitigate DOX drug resistance. DOX was intercalated into nanolamellar hydroxyapatite (LHAp), which was incorporated into electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, and finally, the DOX-intercalated LHAp/PLGA scaffold was coated with polydopamine (PDA) followed by immobilization with siRNA/polyethyleneimine (PEI) complexes. Benefiting from its intrinsic degradability, the scaffold demonstrated pH-responsive release behavior, leading to the simultaneous delivery of DOX and siRNA. Consequently, the codelivery scaffold demonstrated enhanced therapeutic efficiency in vitro and in vivo compared with the scaffold loaded with single drug due to the combined effects of DOX and siRNA and did not show toxicity or side effects in mice. Therefore, it is a safe and effective strategy for preventing postsurgical tumor recurrence.

Easy Synthesis and Characterization of Novel Carbon Dots Using the One-Pot Green Method for Cancer Therapy.

In this study, hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) were used for the synthesis of novel targeted nanocarrier carbon dots (CDC-H) with photo-luminescence using a one-step hydrothermal method. Doxorubicin (DOX), a common chemotherapeutic agent, was loaded with the CDC-H through electrostatic interactions to form DOX-CDC-H complexes as a targeted antitumor drug delivery system. The synthesized CDC-H show a particle size of approximately 6 nm and a high fluorescence quantum yield of 11.64%. The physical and chemical character properties of CDC-H and DOX-CDC-H complexes were investigated using various techniques. The results show that CDC-H have stable luminescent properties and exhibit excellent water solubility. The in vitro release study showed that DOX-CDC-H exhibited pH-dependent release for 24 h. Confocal laser scanning microscopy was applied to investigate the potential of CDC-H for cell imaging and the cellular uptake of DOX-CDC-H in different cells (NIH-3T3 and 4T1 cells), and the results confirmed the target cell imaging and cellular uptake of DOX-CDC-H by specifically binding the CD44 receptors on the surface of tumor cells. The r MTT results suggest that the DOX-CDC-H complex may induce apoptosis in 4T1 cells, reducing the cytotoxicity of free DOX-induced apoptosis. In vivo antitumor experiments of DOX-CDC-H exhibited enhanced tumor cancer therapy. CDC-H have potential applications in bioimaging and antitumor drug delivery.

Formulation of promising antibacterial, anticancer, biocompatible and bioactive biomaterial as therapeutic drug delivery system for biologically active compound loaded on clay polymer

The synthesized heterocyclic compound: 5-[4-bromobenzylidene amino)-1, 3, 4-thiadiazole-2-thiol abbreviated as BATT possessed good antibacterial activity for various Gram-negative and Gram-positive bacteria. In addition to potent antitumor activity to breast cancer, for the first time, the novelty of this study is facile low-cost formulation of safe antitumor drug delivery system (DDS) for breast cancer from such simple heterocyclic compound. Heterocyclic compound is efficiently and spontaneously incorporated into MMT clay polymer matrix forming novel therapeutic nanocomposite DDS for breast cancer. BATT successfully intercalates MMT clay polymer matrix. Electron donation ability of nanocomposites is confirmed by cyclic voltammetry in terms of small peak-to-peak redox potential Delta E_{{{text{peak}}}}. Adsorption of BATT on clay is carried out by batch adsorption method. Better adsorption strength at low pH 2 decreased with increasing pH. Adsorption data are analyzed by multiple mathematical models. MMT clay is an efficient carrier polymer heterogonous adsorbent for BATT at optimum conditions: contact time 2.0 h, pH 2 and initial concentration up to 1200 ppm. Adsorption rate constant, k2 equals 14.6 times 10–3 and qe 19 mg g−1 (R2 0.999). pH of zero charge of MMT at pH 3 reflected adsorption mechanism of MMT. At pH 2, BATT is loaded on MMT by physi- and chemisorption. At pH 4, BATT is loaded on MMT by chemisorption.

Synthesis and Evaluation of Anticancer Activity of Hyaluronic Acid/Vanillin Conjugates

Natural phenolic compounds are known not only for their multiple bioactivities but also for their low bioavailability and rapid metabolism in the systemic circulation. It is well-known that grafting these phenolic compounds to bio-based polymers such as hyaluronic acid (HA), has the advantage to increase their stability and water solubility. HA has CD44 receptors that are overexpressed on cancer cells. This makes from HA an interesting vector for antitumor drug delivery systems. The work reported herein describes the synthesis and the structural characterization of HA/vanillin conjugates as well as the size and shape of their aqueous microassemblies using dynamic light scattering and scattering electron microscopy. Finally, investigation on the bioactivity of such conjugates demonstrates that grafting vanillin to HA improves significantly its cytotoxicity against MDA-MB231 cancer cells in both dose and time-dependent manner, and reduces the migration ability as well as the number and the volume of breast cancer spheres.

Preparation, Characterization, and In Vitro Performance of Gambogic Acid-Layered Double Hydroxide/Liposome Nanocomposites

Gambogic acid (GA) refers to a xanthonoid that exhibits significant antitumor activity due to its poor solubility and low bioavailability. For this reason, its shortcoming should be overcome using novel approaches to improve its practical effectiveness. In this study, with the use of ion exchange method, GA was encapsulated in layered double hydroxide (LDH). In the GA-LDH nanohybrid, GA was distributed and stabilized in the interlamellar region of LDH through intermolecular interactions. GA-LDH was further modified by liposome (LS) through ethanol injection method. The drug encapsulation efficiency of GA-LDH/LS was obtained as 56.28%. The chemical structures and physicochemical properties exhibited by GA-LDH/LS were characterized and confirmed using different instruments, and drug release showed that GA-LDH/LS had significantly sustained release due to the combined effect of the matrix LDH and the phospholipid bilayer. Furthermore, GA-LDH/LS displayed lower hemolysis percentage than GA-LDH during the hemolysis test. This study suggested that GA-LDH/LS nanocomposite could be a promising antitumor drug delivery system due to its outstanding performance in biomedical research.

Research advances in NQO1-responsive prodrugs and nanocarriers for cancer treatment.

NAD(P)H:quinine oxidoreductase (NQO1) is a class of flavoprotein enzymes commonly expressed in eukaryotic cells. It actively participates in the metabolism of various quinones and their in vivo bioactivation through electron reduction reactions. The expression level of NQO1 is highly upregulated in many solid tumor cells compared with that in normal cells. NQO1 has been considered a candidate molecular target because of its overexpression and bioactivity in different tumors. NQO1-responsive prodrugs and nanocarriers have recently been identified as effective objectives for achieving controlled drug release, reducing adverse reactions and improving clinical efficacy. This review systematically introduces the research advances in applying NQO1-responsive prodrugs and nanocarriers to cancer treatment. It also discusses the existing problems and the developmental prospects of these two antitumor drug delivery systems.

Construction of calcium carbonate-liposome dual-film coated mesoporous silica as a delayed drug release system for antitumor therapy

As is well known to all, delivering drug precisely to the tumor site is beneficial to improve antitumor effect. In this study, we reported mesoporous silica nanoparticles (MSNs) coated with dual-film of calcium carbonate (CaCO3) and lipid bilayer (denoted as MSNs@CaCO3@liposomes) innovatively which achieve sustained drug release anchored at tumor microenvironment and enhanced biocompatibility. The pH-sensitive CaCO3 film acted as a guide to cap the pore channels of MSNs allowed pH-triggered drug release when transporting into cancer cells. Furthermore, MSNs@CaCO3 was capsuled by lipid bilayer to improve cellular uptake efficiency and biocompatibility in blood circulation. Morphology of nanoparticles was characterized by transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) to confirm that double films were coated successfully. Doxorubicin hydrochloride (DOX) was efficaciously loaded into mesoporous pores as a model drug with a high drug loading content of 28%, forming DOX-loaded MSNs@CaCO3@liposomes (DOX/MSNs@CaCO3@liposomes). Non-specific protein adsorption and hemolysis test revealed enhanced biocompatibility. Drug release study in vitro showed DOX/MSNs@CaCO3@liposomes could delay to release DOX at pH 5.0 and avoid releasing at pH 7.4. In vitro and in vivo antitumor efficiency evaluation showed that DOX/MSNs@CaCO3@liposomes have a desirable inhibitory activity on tumor growth. Therefore, dual-film coated MSNs could be a good candidate for an antitumor drug delivery system.

PH-Sensitive nanoparticles based on amphiphilic imidazole/cholesterol modified hydroxyethyl starch for tumor chemotherapy

pH-Responsive nanoparticles (NPs) have emerged as an effective antitumor drug delivery system, promoting the drugs accumulation in the tumor and selectively releasing drugs in tumoral acidic microenvironment. Herein, we developed a new amphiphilic modified hydroxyethyl starch (HES) based pH-sensitive nanocarrier of antitumor drug delivery. HES was first modified by hydrophilic imidazole and hydrophobic cholesterol to obtain an amphiphilic polymer (IHC). Then IHC can self-assemble to encapsulate doxorubicin (DOX) and form doxorubicin-loaded nanoparticles (DOX/IHC NPs), which displayed good stability for one week storage and acidic sensitive long-term sustained release of DOX. As a result, cancer cell endocytosed DOX/IHC NPs could continuously release doxorubicin into cytoplasm and nucleus to effectively kill cancer cells. Additionally, DOX/IHC NPs could be effectively enriched in the tumor tissue, showing enhanced tumor growth inhibition effect compared to free doxorubicin. Overall, our amphiphilic modified HES-based NPs possess a great potential as drug delivery system for cancer chemotherapy.