查找使用阿拉丁产品的科研文献

Dual-targeting SERS-encoded graphene oxide nanocarrier for intracellular co-delivery of doxorubicin and 9-aminoacridine with enhanced combination therapy

Hui Chen,Longqiang Xing,Huiru Guo,Caixia Luo,Xuedian Zhang

A graphene oxide (GO)-based nanocarrier that imparts tumor-selective delivery of dual-drug with enhanced therapeutic index, is introduced. GO is conjugated with Au@Ag and Fe3O4 nanoparticles, which facilitates it with SERS tracking and magnetic targeting abilities, followed by the covalent binding of the anti-HER2 antibody, thus allowing it to both actively and passively target SKBR3 cells, human breast cancer cells expressed with HER2. Intracellular drug delivery behaviors are probed using SERS spectroscopy in a spatiotemporal manner, which demonstrates that nanocarriers are internalized into the lysosomes and release the drug in response to the acidic microenvironment. The nanocarriers loaded with dual-drug possess increased cancer cytotoxicity in comparison to those loaded with a single drug. Attractively, the enhanced cytotoxicity against cancer cells is achieved with relatively low concentrations of the drug, which is demonstrated to be involved in the drug adsorption status. These results may give us the new prospects to design GO-based delivery systems with rational drug dosages, thus achieving optimal therapeutic response of the multi-drug with increased tumor selectivity and reduced side effects.

Doxorubicin-loaded hydrogen peroxide self-providing copper nanodots for combination of chemotherapy and acid-induced chemodynamic therapy against breast cancer

Jie-xia Li,Ling-min Zhang,Cheng-cheng Liu,Qian-ni Wu,Song-pei Li,Xue-ping Lei,Yu-gang Huang,Gui-ning Feng,Xi-yong Yu,Xian-qiang Sun,Zhao-ming Guo,Ji-jun Fu

In recent years, chemodynamic therapy (CDT) has gained increasing interest in cancer treatment. In contrast to photodynamic therapy and sonodynamic therapy, extrinsic excitations such as laser or ultrasound are not required in CDT. As a result, the CDT performance is not limited by the penetration depth of the external irritation. However, CDT relies heavily on hydrogen peroxide (H 2 O 2 ) in the tumour microenvironment (TME). Insufficient H 2 O 2 in the TME limits the CDT performance, and the most reported methods to produce H 2 O 2 in the TME are dependent on oxygen supply, which is restricted by the hypoxic TME. In this study, H 2 O 2 self-providing copper nanodots were proposed, and the drug doxorubicin (DOX) was successfully loaded to construct DOX-nanodots. Our results showed that the nanodots produced H 2 O 2 in the weakly acidic TME due to the peroxo group and further generated the most active hydroxyl radical ( OH) through the Fenton-like reaction. This process was pH-dependent and did not occur in a neutral environment. In addition to OH, the nanodots also produced singlet oxygen ( 1 O 2 ) and superoxide anions (O 2 – ) in the cancer cells. The copper nanodots performed promising CDT against breast cancer in vitro and in vivo, with enhanced cell apoptosis and decreased cell proliferation . The combination of chemotherapy and CDT using DOX-nanodots further improved the therapeutic effects. The treatments showed good biocompatibility with no obvious toxicity in major tissues, possibly due to the specific OH generation in the weakly acidic TME. In summary, the H 2 O 2 self-providing copper nanodots in combination with DOX showed promising cancer-curing effects due to the oxygen-independent and tumour-specific production of reactive oxygen species and the cooperation of chemotherapy.

Facile strategy by hyaluronic acid functional carbon dot-doxorubicin nanoparticles for CD44 targeted drug delivery and enhanced breast cancer therapy

Jianping Li,Man Li,Lifeng Tian,Yue Qiu,Qianwen Yu,Xuhui Wang,Rong Guo,Qin He

A facile approach was developed to synthesize an innovative hyaluronic acid-modified carbon dot-doxorubicin nanoparticles drug delivery platform. CD44 targeted HA-modified carbon dots (HA-CDs) were synthesized as carrier by one-step hydrothermal treatment within one hour with citric acid and branch-PEI as core carbon source. HA not only functioned as carbon dot component but also as hydrophilic group and targeting ligand of this system. The as-prepared HA-CDs were then loaded with doxorubicin (HA-CD@p-CBA-DOX) via an acid-cleavable bond, which released drug in a pH-responsive manner. In in vitro experiments, HA-CD@p-CBA-DOX displayed good hemocompatibility and serum stability, while exhibited high cytotoxicity on 4T1 cells. The confocal laser scanning microscopy and flow cytometry results demonstrated that DOX-loaded nanoparticles were internalized by 4T1 cells via HA-mediated CD44-targeting effect. The enhanced in vivo tumor accumulation of HA-CD@p-CBA-DOX was testified by live imaging. Compared with free DOX, superior in vivo anti-tumor efficacy of HA-CD@p-CBA-DOX was observed in both heterotopic and orthotopic 4T1 cell tumor models. Furthermore, blood hematology and blood biochemistry analysis demonstrated that HA-CD@p-CBA-DOX did not induce noticeable toxicity, which further confirmed the good biocompatibility of HA-CD@p-CBA-DOX. The formulated HA-CD@p-CBA-DOX provides an alternative strategy for targeted breast cancer therapy.

Synergistically Enhanced Inhibitory Effects of Pullulan Nanoparticle-Mediated Co-Delivery of Lovastatin and Doxorubicin to Triple-Negative Breast Cancer Cells

Wu Di,Chen Yao,Wen Shun,Wen Yi,Wang Rong,Zhang Qiuting,Qin Ge,Yi Huimei,Wu Mi,Lu Lu,Tao Xiaojun,Deng Xiyun

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is prone to drug resistance and difficult to treat. In this study, we grafted water-soluble pullulan with lovastatin (LV) to develop a novel amphiphilic conjugate, pullulan-encapsulated LV (PLV). The PLV conjugate was synthesized with three different ratios of pullulan to LV and characterized by Fourier transform infrared (FTIR). The degree of substitution (DS) of LV in terms of molar ratio was 7.87%, 3.58%, and 3.06% for PLV (1/2), PLV (1/3), and PLV (1/4), respectively, by proton NMR analysis. We selected the PLV (1/2) conjugate to prepare doxorubicin (DXR)-loaded PLV nanoparticles (PLV/DXR NPs) because of its superior properties. The average size and zeta potential for PLV (1/2) NPs were 177.6 nm and − 11.66 mV, respectively, determined by dynamic light scattering, and those for PLV/DXR NPs were 225.6 nm and − 10.51 mV, respectively. In vitro drug release profiling showed that PLV/DXR NPs sustainably released DXR within 72 h, which was more robust at pH 5.4 (97.90%) than pH 7.4 (76.15%). In the cytotoxicity study, PLV/DXR NPs showed greater inhibition of proliferation of TNBC MDA-MB-231 than non-TNBC MDA-MB-453 cells (IC 50 0.60 vs 11.05 μM). FITC-loaded PLV/DXR NPs were prepared to investigate cellular uptake: both cell lines showed a time-dependent uptake of NPs, but the number of NPs entering MDA-MB-231 cells was greater than that entering the MDA-MB-453 cells. Pullulan-based NP co-delivery of LV and DXR could efficiently inhibit TNBC cells, which may help in designing a powerful drug delivery system for treating TNBC.

Co-encapsulation of magnetic Fe3O4 nanoparticles and doxorubicin into biocompatible PLGA-PEG nanocarriers for early detection and treatment of tumours

Chenghua Liang,Nan Li,Zikai Cai,Rongpu Liang,Xiaoming Zheng,Li Deng,Longbao Feng,Rui Guo,Bo Wei

At present, cancer is the first cause of death for humans, but early detection and treatment can help improve prognoses and reduce mortality. However, further development of carrier-assistant drug delivery systems (DDSs) is retarded by the aspects such as the low drug-carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. The development of nanoscale drug delivery systems (NDDS) have been rapidly developed to address these issues. In this article, we used PLGA-PEG with good biocompatibility to encapsulate Fe3O4 nanoparticles (a magnetic resonance imaging contrast agent) and DOX (an antitumour drug) via the emulsion-solvent evaporation method, aimed at achieving a dual function of the early detection and the treatment of mammary cancer. The results showed that the Fe3O4/DOX/PLGA-PEG nanoparticles had a relatively uniform size, a high carrier rate of Fe3O4 and high encapsulation efficiency of DOX, and a relatively high activity of released DOX within 120 h. In addition, in vitro studies showed that the Fe3O4/DOX/PLGA-PEG nanoparticles were cytocompatibility in NIH 3T3 fibroblast cells culture study while had a special effect on destroying human breast cancer MCF-7 cells compared with pure DOX solution. In vitro studies revealed that the Fe3O4/DOX/PLGA-PEG enabled enhanced T2 contrast magnetic resonance. Overall, our multifunctional Fe3O4/DOX/PLGA-PEG nanoparticles, composed of biocompatible substances and therapeutic/imaging materials, have great potential for the early detection of cancer and accurate drug delivery via the dynamic monitoring using MRI.

pH-Triggered Charge-Reversal Mesoporous Silica Nanoparticles Stabilized by Chitosan Oligosaccharide/Carboxymethyl Chitosan Hybrids for Effective Intracellular Delivery of Doxorubicin

Lan Cui,Wentao Liu,Hao Liu,Qian Qin,Shuangxia Wu,Suqin He,Xinchang Pang,Chengshen Zhu,Peihong Shen

Surface modification of mesoporous silica nanoparticles (MSNs) is a promising way to enhance therapeutic efficacy and minimize side effects of anticancer drugs. In this work, MSNs with reduced particle size and optimum pore diameter were obtained and catalyzed by ammonia/triethanolamine. In view of the negatively charged carboxymethyl chitosan (CMC) and positively charged chitosan oligosaccharide (CS), the pH-triggered charge-reversal CS/CMC bilayer was designed as a stimuli-responsive switch for MSNs via the protonation and deprotonation effect. The results showed that MSNs-CS/CMC were core–shell and mesoporous in structure. Surface charge conversion and pH dependence were clearly observed in the doxorubicin hydrochloride (DOX) delivery. The intracellular uptake indicated that DOX@MSNs-CS/CMC could be distributed in the cytoplasm of MCF-7 cells and exhibited lower toxicity, which would improve the stability and prolong the retention time compared to free DOX and unmodified DOX@MSNs at pH 7.4. Moreover, the cellular uptake and internalization of DOX@MSNs-CS/CMC were enhanced to promote drug delivery into the cell nucleus at pH 6.5. The biocompatible and surface-charge-reversible MSNs-CS/CMC have the potential to prolong the retention time in the bloodstream, facilitate the endosome escape, and enrich the targeted antitumor strategy, providing an alternative platform for efficient drug delivery in breast cancer therapy.

Ratiometric co-encapsulation and co-delivery of doxorubicin and paclitaxel by tumor-targeted lipodisks for combination therapy of breast cancer

Chunlai Feng,Haisheng Zhang,Jiaming Chen,Siqi Wang,Yuanrong Xin,Yang Qu,Qi Zhang,Wei Ji,Fumiyoshi Yamashita,Mengjie Rui,Ximing Xu

Combination therapy is a promising treatment for certain advanced drug-resistant cancers. Although effective inhibition of various tumor cells was reported in vitro , combination treatment requires improvement in vivo due to uncontrolled ratiometric delivery. In this study, a tumor-targeting lipodisk nanoparticle formulation was developed for ratiometric loading and the transportation of two hydrophobic model drugs, doxorubicin (DOX) and paclitaxel (PTX), in one single platform. Furthermore, a slightly acidic pH-sensitive peptide (SAPSP) incorporated into lipodisks effectively enhanced the tumor-targeting and cell internalization. The obtained co-loaded lipodisks were approximately 30  nm with a pH-sensitive property. The ratiometric co-delivery of two drugs via lipodisks was confirmed in both the drug-resistant MCF-7/ADR cell line and its parental MCF-7 cell line in vitro , as well as in a tumor-bearing mouse model in vivo compared with a cocktail solution of free drugs. Co-loaded lipodisks exerted improved cytotoxicity to tumor cells in culture, particularly to drug-resistant tumor cells at synergistic drug ratios. In an in vivo xenograft mouse model, the anti-tumor ability of co-loaded lipodisks was evidenced by the remarkable inhibitory effect on tumor growth of either MCF-7 or MCF-7/ADR tumors, which may be attributed to the increased and ratiometric accumulation of both drugs in the tumor tissues. Therefore, tumor-specific lipodisks were crucial for the combination treatment of DOX and PTX to completely exert a synergistic anti-cancer effect. It is concluded that for co-loaded lipodisks, cytotoxicity data in vitro could be used to predict their inhibitory activity in vivo , potentially enhancing the clinical outcome of synergistic therapy.

MIL-100(Al) Gels as an Excellent Platform Loaded with Doxorubicin Hydrochloride for pH-Triggered Drug Release and Anticancer Effect

Yuge Feng,Chengliang Wang,Fei Ke,Jianye Zang,Junfa Zhu

Slow and controlled release systems for drugs have attracted increasing interest recently. A highly efficient metal-organic gel (MOGs) drug delivery carrier, i.e., MIL-100(Al) gel, has been fabricated by a facile, low cost, and environmentally friendly one-pot process. The unique structure of MIL-100(Al) gels has led to a high loading efficiency (620 mg/g) towards doxorubicin hydrochloride (DOX) as a kind of anticancer drug. DOX-loaded MOGs exhibited high stability under physiological conditions and sustained release capacity of DOX for up to three days (under acidic environments). They further showed sustained drug release behavior and excellent antitumor effects in in vitro experiments on HeLa cells, in contrast with the extremely low biotoxicity of MOGs. Our work provides a promising way for anticancer therapy by utilizing this MOGs-based drug delivery system as an efficient and safe vehicle.Keywords:metal-organic gels;doxorubicin loading and release;pH-responsiveness;anticancer effect

Co-delivery of doxorubicin and shRNA of Beclin1 by folate receptor targeted pullulan-based multifunctional nanomicelles for combinational cancer therapy

Lili Chen,Ming Qian,Liuwei Zhang,Jing Xia,Yongming Bao,Jingyun Wang,Lianying Guo,Yachen Li

Doxorubicin (DOX) is a widely-used effective antitumor agent. However, its clinical application is limited due to its side effects including anti-apoptotic defense of cancer cells caused by DOX-induced autophagy and deleterious effects in normal tissues. Therefore, in this study, a new folate (FA)-decorated amphiphilic bifunctional pullulan-based copolymer (named as FPDP) was developed as an efficient nano-carrier for the co-delivery of DOX and short hairpin RNA of Beclin1, a pivotal autophage-related gene, to enhance the anticancer effect of DOX by the blockade of the Beclin1 protein mediated autophagy process. In FPDP molecules, pullulan was modified with lipophilic desoxycholic acid for the formation of micelles, the introduced low molecular weight (1 kDa) branched polyethylenimine (PEI) was for shBeclin1 delivery, and folate (FA) was employed as the tumor-targeting group. FPDP micelles demonstrated an average diameter of 161.9 nm, good biocompatibility, applicable storage stability, excellent loading capacities for both DOX and shBeclin1 and a sustained drug release profile. In vitro cell culture experiments demonstrated that the uptake amount of FPDP/DOX micelles in folate receptor positive (FR+) HeLa cells was more than that in folate receptor negative (FR−) HepG2 cells, leading to significantly higher cytotoxicity against FR+ HeLa cells. The simultaneous co-delivery of shBeclin1 and DOX to HeLa cells with FPDP micelles led to efficient reduction in the expression level of Beclin1 as well as synergistic cell apoptotic induction. Furthermore, in vivo studies revealed superior antitumor efficacy of tumor-targeted FPDP/DOX/shBeclin1 in comparison with non-FR-targeted PDP micelles and free DOX. These results highlighted that co-delivery of DOX and shRNA of Beclin1 with FPDP micelles has the potential to overcome the limitations of DOX in clinical cancer therapy.

Liposome-based codelivery of celecoxib and doxorubicin hydrochloride as a synergistic dual-drug delivery system for enhancing the anticancer effect

Kamel S. Ahmed,Sun Changling,Xiaotian Shan,Jing Mao,Lipeng Qiu,Jinghua Chen

Polymeric nanovesicles as simultaneous delivery platforms with doxorubicin conjugation and elacridar encapsulation for enhanced treatment of multidrug-resistant breast cancer

Hong Xiao,Jin He,Xiaoxia Li,Bo Li,Lu Zhang,Yong Wang,Du Cheng,Xintao Shuai

Multidrug resistance (MDR) is one of the major obstacles hindering the successful chemotherapy of cancer. Overexpression of drug efflux transporters such as P-glycoprotein (P-gp) is an important factor responsible for MDR. In this study, a novel copolymer methoxy-poly(ethylene glycol)–poly[(N-(6-hydroxyhexyl)-g-doxorubicin-L-aspartamide)-(β-benzyl-L-aspartate)] (mPEG-P[Asp(HPA-g-DOX)-BLA)] was synthesized and utilized to assemble into nanovesicles with hydrophilic P-gp inhibitor elacridar hydrochloride (Ela) encapsulated into the aqueous lumen. Doxorubicin (DOX) was covalently conjugated onto the polymer chain via a pH-cleavable amide linkage, leading to a pH responsive DOX release as well as disintegration of the nanovesicles in the lysosome of tumor cells. In vitro studies demonstrated that the DOX and Ela co-delivered nanovesicles showed superior cytotoxicity and enhanced anti-tumor properties as compared to single DOX-delivery nanosystems in MCF-7/ADR cancer, which was attributed to the P-gp bioactivity inhibition as investigated by a cell immunofluorescence assay. In vivo studies showed that the polymeric nanovesicles effectively accumulated at the tumor site and the co-delivered DOX and Ela effectively suppressed the MCF-7/ADR tumor growth. All the results indicated that the acid-liable nanovesicles had a synergistic effect to enhance antitumor efficacy for multidrug-resistant breast cancer treatment.

Chemoresistance to doxorubicin induces epithelial-mesenchymal transition via upregulation of transforming growth factor β signaling in HCT116 colon cancer cells

Jinpeng Li,Hao Liu,Jieping Yu,Honggang Yu

Doxorubicin (Dox) is a commonly used chemotherapeutic drug in human colon cancer. However, it becomes increasingly ineffective with tumor progression, the underlying mechanism of which remains to be elucidated. Emerging evidence has led to the identification of an association between chemoresistance and the acquisition of epithelial‑mesenchymal transition (EMT) in cancer. However, it remains to be elucidated whether this process is involved in the development of resistance to Dox in colon cancer. In HCT116 human colon cancer cells treated with Dox (50 nmol/l), EMT was induced, and transforming growth factor (TGF)β signaling and multi‑drug resistant plasma membrane glycoprotein levels were significantly increased. By contrast, silencing of Smad4, using stable RNA interference, inhibited TGFβ signaling, reversed the process of EMT and markedly increased the sensitivity of HCT116 cells to Dox. The results of the present study suggested that the combination of Dox with the downregulation of TGFβ signaling may be a potential novel therapeutic strategy with which to overcome chemoresistance during colon cancer chemotherapy.