The effect of poloxamer 188 on nanoparticle morphology,size, cancer cell uptake,and cytotoxicity

The aim of this work was to investigate the effect of triblock copolymer poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity. Docetaxel-loaded nanoparticles were prepared by oil-in-water emulsion/solvent evaporation technique using biodegradable poly(lactic-co-glycolic acid) (PLGA) with or without addition of poloxamer 188, respectively. The resulting nanoparticles were found to be spherical with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug-release profile of both nanoparticle formulations showed a biphasic release pattern. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in the docetaxel-resistant MCF-7 TAX30 human breast cancer cell line could be found in comparison with that of PLGA nanoparticles. In addition, the docetaxel-loaded PLGA/poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than that of docetaxel-loaded PLGA nanoparticles and Taxotere (P < .05). In conclusion, the results showed advantages of docetaxel-loaded PLGA nanoparticles incorporated with poloxamer 188 compared with the nanoparticles without incorporation of poloxamer 188 in terms of sustainable release and efficacy in breast cancer chemotherapy.From the Clinical EditorThe effects of poloxamer 188, a triblock copolymer were studied on nanoparticle morphology, size, cancer cell uptake and cytotoxicity. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in resistant human breast cancer cell line was demonstrated, resulting in a significantly higher level of cytotoxicity.     

Quercetin-loaded poly (lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for the targeted treatment of liver cancer

Utilization of quercetin (QT) in clinics is limited by its instability and poor solubility. To overcome these disadvantages, we prepared QT as QT-loaded PLGA-TPGS nanoparticles (QPTN) and examined its properties and therapeutic efficacy for liver cancer. QT-loaded PLGA nanoparticles (QPN) and QT/coumarin-6-loaded PLGA-TPGS nanoparticles (QCPTN) with coumarin-6 as a fluorescent marker were also prepared to investigate the cellular uptake by HepG2 and HCa-F cells using a confocal laser scanning microscope (CLSM), and their effects on apoptosis of HepG2 cells were assessed with flow cytometry. The results measured using transmission electron microscopy, scanning electron microscopy and size analyses indicated that QPTN were stably dispersed sphere with diameter in the range of 100-200?nm. It indicated that the QT loading and encapsulation efficiency in QPTN reached 21.63% and 93.74%, respectively, and the accumulative drug release of QPTN was 85.8%, the QCPTN uptake in HCa-F and HepG2 cells were 50.87% and 61.09% using HPLC analysis, respectively. The results determined using an Annexin-PI flow cytometry indicated that QPTN could induce HepG2 cell apoptosis in a dose dependent manner. The results of histological examination and HPLC analysis confirmed that QPTN was targeted to liver cells. In vivo analysis using solid tumor-bearing mouse model indicated that QPTN could suppress tumor growth by 59.07%. Moreover, all the studied properties of QPTN were more desirable than those of QT-loaded PLGA nanoparticles (QPN). In conclusion, QPTN could be used as a potential intravenous dosage form for the treatment of liver cancer owing to the enhanced pharmacological effects of QT with increased liver targeting.     

TRAIL and curcumin codelivery nanoparticles enhance TRAIL-induced apoptosis through upregulation of death receptors

Active targeting nanoparticles were developed to simultaneously codeliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Curcumin (Cur). In the nanoparticles (TRAIL-Cur-NPs), TRAIL was used as both active targeting ligand and therapeutic agent, and Cur could upregulate death receptors (DR4 and DR5) to increase the apoptosis-inducing effects of TRAIL. Compared with corresponding free drugs, TRAIL-Cur-NPs group showed enhanced cellular uptake, cytotoxicity and apoptosis induction effect on HCT116 colon cancer cells. In addition, in vivo anticancer studies suggested that TRAIL-Cur-NPs had superior therapeutic effect on tumors without obvious toxicity, which was mainly due to the high tumor targeting and synergistic effect of TRAIL and Cur. The synergistic mechanism of improved antitumor efficacy was proved to be upregulation of DR4 and DR5 in tumor cells induced by Cur. Thus, the prepared codelivery nanoparticles may have potential applications in colorectal cancer therapy.     

Folate-receptor-targeted delivery of docetaxel nanoparticles prepared by PLGA–PEG–folate conjugate

For folate-receptor-targeted anticancer therapy, docetaxel (DTX) nanoparticles (NPs) were produced employing polylactide-co-glycolide–polyethylene glycol–folate (PLGA–PEG–FOL) conjugate. The FOL-conjugated di-block copolymer was synthesized by coupling the PLGA–PEG–NH₂ di-block copolymer with an activated folic acid. It was expected that FOL moieties were exposed on the micellar surface.

The conjugates assisted in the formation of DTX NPs with an average size of 200 nm in diameter through an emulsification/solvent diffusion method. The FOL-targeted NPs showed a greater extent of intracellular uptake in FOL-receptor-positive cancer cells (SKOV3) in comparison with the non-targeted NPs, indicating that the FOL-receptor-mediated endocytosis mechanism could have a role in the cellular uptake of NPs. These results suggested that FOL-targeted DTX NPs could be a potentially useful delivery system for FOL-receptor-positive cancer cells.     

泊洛沙姆188-PLGA纳米给药系统对抗耐药肿瘤的研究

目的 利用泊洛沙姆188对PLGA进行化学修饰,制备包载阿霉素的纳米粒,并评价纳米粒在人耐药乳腺癌细胞中的摄取能力及毒性。方法 通过EDC/NHS法合成泊洛沙姆188-PLGA,通过核磁共振对其结构进行表征并测定临界胶束浓度;通过纳米沉淀法制备包载阿霉素的纳米粒,通过粒度仪对纳米粒的粒径及分布进行分析,通过细胞摄取实验及细胞毒性实验对纳米粒的摄取效果及毒性进行评价。结果 成功合成了泊洛沙姆188-PLGA,并制备了粒径在140 nm左右的纳米粒,该纳米粒在人耐药乳腺癌细胞中有较好的摄取效果及较强的毒性。结论 泊洛沙姆188能够逆转耐药,增强耐药细胞对化疗药物的敏感程度。     

葫芦素B-聚乳酸-羟基乙酸共聚物载药纳米粒的构建与药效学评价

目的 以聚乳酸-羟基乙酸共聚物（PLGA）作为纳米制剂载体材料将葫芦素B制备成纳米粒,并考察其对HepG2肝癌细胞的抑制效果。方法 使用乳化溶剂蒸发法制备葫芦素B-PLGA载药纳米粒,以PLGA浓度（X₁）、PVA浓度（X₂）和药物浓度（X₃）作为考察因素,以载药纳米粒的粒径大小（Y₁）和包封率（Y₂）作为评价指标,应用中心复合设计-效应面法优化葫芦素B-PLGA载药纳米粒处方;测定了纳米粒的粒径分布和Zeta电位值,通过透射电镜观察其微观形态,并考察了葫芦素B-PLGA载药纳米粒的体外药物释放特性;比较了葫芦素B与葫芦素B-PLGA载药纳米粒对HepG2肝癌细胞的抑制效果。结果 葫芦素B-PLGA载药纳米粒的最优处方组成为：PLGA浓度为9.0%,PVA浓度为2.0%,药物浓度为4.5%,制备的纳米粒粒径为（145.4±15.8） nm,Zeta电位值为（-7.6±0.8） mV;透射电镜下可观察到纳米粒表面光滑,分布均匀;葫芦素B-PLGA载药纳米粒释药前期出现突释,后期平缓,48 h药物释放达到86%;葫芦素B-PLGA载药纳米粒对HepG2肝癌细胞的抑制作用显著高于葫芦素B。结论 葫芦素B-PLGA载药纳米粒可延缓药物释放,提高对HepG2肝癌细胞的抑制活性,为进一步临床研究奠定实验基础。     

Comparative study of kanamycin sulphate microparticles and nanoparticles for intramuscular administration: preparation in vitro release and preliminary in vivo evaluation

Kanamycin sulphate (KS) is a Mycobacterium tuberculosis protein synthesis inhibitor. KS is polycationic, a property responsible for KS poor oral absorption half-life (2.5?h) and rapid renal clearance, which results in serious nephrotoxicity/ototoxicity. The current study aimed to develop KS-loaded PLGA vitamin-E-TPGS microparticles (MPs) and nanoparticles (NPs) to reduce the dosing frequency and dose-related adverse effect. In vitro release was sustained up to 10 days for KS PLGA–TPGS MPs and 13 days for KS PLGA–TPGS NPs in phosphate-buffered saline (PBS) pH 7.4. The in vivo pharmacokinetic test in Wistar rats showed that the AUC_0–∞ of KS PLGA–TPGS NPs (280.58?μg/mL*min) was about 1.62-fold higher than that of KS PLGA–TPGS MPs (172.30?μg/mL*min). Further, in vivo protein-binding assay ascribed 1.20-fold increase in the uptake of KS PLGA–TPGS NPs through the alveolar macrophage (AM). The studies, therefore, could provide another useful tool for successful development of KS MPs and NPs.     

In Vitro and In Vivo Study of Gal-OS Self-Assembled Nanoparticles for Liver-Targeting Delivery of Doxorubicin

A liver-targeting drug delivery system for doxorubicin (DOX), that is, DOX-loaded self-assembled nanoparticles based on galactosylated O-carboxymethyl chitosan-graft-stearic acid conjugates (Gal-OS/DOX), has been prepared. The objective of the present study was to investigate the preparation, in vitro release, in vivo pharmacokinetics, and tissue distribution of Gal-OS/DOX nanoparticles. The drug-loaded nanoparticles were spherical in shape with mean size of 181.9 nm. In vitro release profiles indicated that the release of DOX from Gal-OS/DOX nanoparticles behaved with a sustained and pH-dependent drug release. Pharmacokinetics study revealed Gal-OS/DOX nanoparticles exhibited a higher AUC value and a prolonged residence time of drug in the blood circulation than those of DOX solution. Furthermore, Gal-OS/DOX nanoparticles increased the uptake of DOX in liver and spleen, but decreased uptake in heart, lung, and kidney in the tissue distribution study. These results suggested that the Gal-OS/DOX nanoparticles could prolong blood circulation time, enhance the liver accumulation, and reduce the side effect especially the cardiotoxicity of DOX. In conclusion, Gal-OS/DOX nanoparticles could be a promising drug delivery system for liver cancer therapy.     

MUC1 aptamer-targeted DNA micelles for dual tumor therapy using doxorubicin and KLA peptide

Targeted delivery of DNA nanoparticles is a promising approach in cancer therapy. Using aptamers, target specific delivery of DNA nanoparticles can be achieved. Further, aptamers can indirectly improve drug encapsulation efficiency of DNA nanoparticles for drugs intercalated within nucleic acid base pairs. Using DNA blocks, a micellar hybrid nanoparticle was prepared for the targeted co-delivery of doxorubicin and a pro-apoptotic peptide, KLA to tumor cells. Results demonstrated that anti-MUC1 aptamer could specifically deliver the synthesized DNA micelle into MCF-7 cells by improving its cellular uptake. Additionally, co-delivery of doxorubicin and KLA could significantly enhance the therapeutic efficacy of the construct resulting in reduction of required dose of doxorubicin that is a pivotal point in reducing chemotherapeutics side effects. Moreover, DOX–KLA–anti-MUC1–micelle remarkably inhibited tumor growth of tumor-bearing mice when compared with free drug. DOX–KLA–anti-MUC1–micelle also reduced toxic effect of free doxorubicin as determined by percent of body weight loss and survival rate in vivo.     

Investigation of the interaction of biodegradable micro‐ and nanoparticulate drug delivery systems with platelets

Objectives Biodegradable micro‐ and nanoparticles are being increasingly investigated for drug delivery and targeting of therapeutics. The size and surface properties of these particles are important factors influencing their interaction and uptake by various cells, tissues and organs. Optimising these properties, to enhance cellular uptake, may increase their potential for interaction with other physiological components such as platelets resulting in platelet activation and inappropriate thrombus formation. The aim of this study was to investigate the potential interaction of particulates with platelets. Methods Biodegradable micro‐ and nanoparticles based on poly‐lactide‐co‐glycolide (PLGA), poly‐lactide‐co‐glycolide–macrogol (PLGA‐macrogol) and chitosan were prepared using solvent evaporation, spray drying or solvent dispersion techniques. Key findings Microparticles formulated had a median diameter (D50%) of 2–9 µm, while nanoparticles had an average diameter of 100–500 nm. The surface morphology ranged from smooth and spherical to irregular depending on polymer and preparation method used. Particles, reconstituted in the concentration range of 0.1–500 µg/ml, were tested for their ability to induce or inhibit platelet aggregation. No effects on either induction of platelet activity or inhibition of aggregation were detected. Conclusions None of the particles examined were found to alter platelet activity. These results suggested that the biodegradable micro‐ and nanoparticles tested were safe for use as potential drug carriers of therapeutic agents.     

Cellular delivery of PEGylated PLGA nanoparticles

Objectives The objective of this study was to investigate the efficiency of uptake of PEGylated polylactide‐co‐gycolide (PLGA) nanoparticles by breast cancer cells. Methods Nanoparticles of PLGA containing various amounts of polyethylene glycol (PEG, 5%–15%) were prepared using a double emulsion solvent evaporation method. The nanoparticles were loaded with coumarin‐6 (C6) as a fluorescence marker. The particles were characterized for surface morphology, particle size, zeta potential, and for cellular uptake by 4T1 murine breast cancer cells. Key findings Irrespective of the amount of PEG, all formulations yielded smooth spherical particles. However, a comparison of the particle size of various formulations showed bimodal distribution of particles. Each formulation was later passed through a 1.2 µm filter to obtain target size particles (114–335 nm) with zeta potentials ranging from ?2.8 mV to ?26.2 mV. While PLGA‐PEG di‐block (15% PEG) formulation showed significantly higher 4T1 cellular uptake than all other formulations, there was no statistical difference in cellular uptake among PLGA, PLGA‐PEG‐PLGA tri‐block (10% PEG), PLGA‐PEG di‐block (5% PEG) and PLGA‐PEG di‐block (10% PEG) nanoparticles. Conclusion These preliminary findings indicated that the nanoparticle formulation prepared with 15% PEGylated PLGA showed maximum cellular uptake due to it having the smallest particle size and lowest zeta potential.     

Studies on bioadhesive PLGA nanoparticles: A promising gene delivery system for efficient gene therapy to lung cancer

The study aimed to design novel bioadhesive PLGA nanoparticles for efficient gene delivery to lung cancer cells. The bioadhesive agent and stabilizer, Carbopol 940 was chosen to establish bioadhesive PLGA nanoparticles and Pluronic F68, Pluronic F127 stabilized PLGA nanoparticles were formulated as control. The effects of different surfactants on the physicochemical and biological characterizations of PLGA nanoparticles were compared. All the obtained nanoparticles showed negative surface charge, similar spherical morphology, a relatively narrow particle size distribution, and lower cytotoxicity to A549 cells comparing with Lipofectamine 2000. Carbopol stabilized nanoparticles hold advantages in DNA-binding efficiency (>80%) at an optimal Carbopol concentration, DNA protection from enzymatic degradation in vitro release and better buffering capacity. Most importantly, higher transfection efficiency in A549 cells was observed comparing to Pluronics stabilized nanoparticles or naked DNA, similar to that of Lipofectamine 2000. These results revealed that the bioadhesive PLGA nanoparticles formulated with Carbopol might be a very attractive candidate as a non-viral vector for lung cancer gene therapy and might alleviate the drawbacks of the conventional cationic vectors/DNA complexes for gene delivery in vivo.     

Octreotide-conjugated PAMAM for targeted delivery to somatostatin receptors over-expressed tumor cells

Abstract

Purpose: An octreotide-conjugated polyamidoamine (PAMAM) dendrimer was synthesized and employed as nanocarriers of methotrexate (MTX), for targeting to the somatostatin receptors over-expressed tumor cells.

Methods: PAMAM–PEG–octreotide (PPO) and PAMAM–PEG (PPG) were synthesized and characterized. The cellular uptake of fluorescein isothiocyanate (FITC)-labeled PPO (PPO-FITC) and PPG (PPG-FITC) were investigated. The cytotoxicity of MTX and MTX nanoparticles were conducted in the MCF-7 cells. Besides, the pharmacokinetics studies on MTX nanoparticles were carried out in rats.

Results: The structure of PPO was verified by NMR detection and the diameter was 11.05?±?1.80?nm, with the amount of MTX encapsulated by PPO was 30?(molecule/molecule). MTX nanoparticles possessed significantly higher cytotoxicity against MCF-7 cells compared with free MTX, especially the PPO/MTX nanoparticles. Correspondingly, the PPO-FITC carrier had higher cellular uptake efficiency compared to PPG-FITC. In addition, pharmacokinetics studies showed that PPO/MTX nanoparticles increased mean residence time and bioavailability of MTX distinctly.

Discussion and conclusion: With further cellular uptake test of FITC-labeled carriers, the enhanced cytotoxicity of PPO/MTX nanoparticles was reasonable to ascribe to the specific receptor-mediated endocytosis induced by octreotide. The present study suggests that this PAMAM–PEG–octreotide nanocarrier opens a new path for treating cancer with higher efficacy.     

Uptake and bioconversion of stereoisomeric dipeptide prodrugs of ganciclovir by nanoparticulate carriers in corneal epithelial cells

Purpose: The objective of this study is to investigate cellular uptake of prodrug-loaded nanoparticle (NP). Another objective is to study bioconversion of stereoisomeric dipeptide prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and d-Val-l-Val-GCV (DLGCV) in human corneal epithelial cell (HCEC) model.

Methods: Poly(_D,L-lactic-co-glycolic acid) (PLGA) NP encapsulating prodrugs of GCV were formulated under a double emulsion method. Fluorescein isothiocyanate isomer–PLGA conjugates were synthesized to fabricate biocompatible fluorescent PLGA NP. Intracellular uptake of FITC-labeled NP was visualized by a fluorescent microscope in HCEC cells.

Results: Fluorescent PLGA NP and non-fluorescent NP display similar hydrodynamic diameter in the range of 115–145?nm with a narrow particle size distribution and zeta potentials around ?13 mV. Both NP types showed identical intracellular accumulation in HCEC cells. Maximum uptake (around 60%) was noted at 3?h for NP. Cellular uptake and intracellular accumulation of prodrugs are significantly different among three stereoisomeric dipeptide prodrugs. The microscopic images show that NPs are avidly internalized by HCEC cells and distributed throughout the cytoplasm instead of being localized on the cell surface. Following cellular uptake, prodrugs released from NP gradually bioreversed into parent drug GCV. LLGCV showed the highest degradation rate, followed by LDGCV and DLGCV.

Conclusion: LLGCV, LDGCV and DLGCV released from NP exhibited superior uptake and bioreversion in corneal cells.     

Glypican-3 gene silencing for ovarian cancer using siRNA-PLGA hybrid micelles in a murine peritoneal dissemination model

Small interfering RNA (siRNA) has received much attention and for possible therapeutic applications to treat incurable chronic and genetic diseases, including cancer. However, the development of safe and efficient carriers for siRNA delivery still remains formidable hurdles for in vivo. The purpose of this study is to prepare siRNA–PLGA hybrid micelles to deliver the siRNA into the ovarian cancer cells and to evaluate of gene silencing effects in mice model. Here we focused on glypican-3 (Gpc3) gene silencing, which involved in tumor progression and inflammatory reaction, as a siRNA target in a murine ovarian cancer cells, HM-1. As a result, linear polyethyleneimine (LPEI)-coated siRNA–PLGA hybrid micelles were shown to effectively inhibit GPC3 expression in vitro in HM-1 cells, compared with siRNA in solution, because of their superior intracellular uptake and enhanced gene silencing effects. In addition, intraperitoneal administration of the cationic LPEI-coated siRNA–PLGA hybrid micelles decreased the number of tumor nodes in the mesentery, compared with the siRNA sole solution, in a HM-1 peritoneal dissemination model. These results suggested that siRNA–PLGA hybrid micelles could be an effective siRNA delivery tool in a murine ovarian cancer model, especially in case it targets molecules, such as Gpc3.     

Mannosylated nanoparticulate carriers of rifabutin for alveolar targeting

The objective of the present study was to evaluate the prospective of engineered nanoparticles for selective delivery of an antituberculosis drug, rifabutin, to alveolar tissues. Drug-loaded solid lipid nanoparticles (SLNs) were synthesized and efficiently mannosylated. The formation of uncoated and coated SLNs was characterized by FTIR spectroscopy and SEM studies. A variety of physicochemical parameters such as drug loading, particle size, polydispersity index, zeta potential, and in vitro drug release were determined. The toxicity and targeting potential of the prepared formulation were assessed with alveolar macrophage uptake, hematological studies, and in vivo studies of uncoated and coated SLNs. Ex vivo cellular uptake studies of SLNs formulations in alveolar macrophages depicted almost six times enhanced uptake due to mannose coating. The hematological studies proved mannose-conjugated system to be less immunogenic and suitable for sustained delivery as evaluated against uncoated formulation. Further, the serum level and organ distribution studies demonstrated efficiency of the system for prolonged circulation and spatial delivery of rifabutin to alveolar tissues. Finally, it was concluded that mannose-conjugated SLNs can be exploited for effective and targeted delivery of rifabutin compared to its uncoated formulation and ultimately increasing the therapeutic margin of safety while reducing the side effects.     

Hydrophobic binding peptide-conjugated hybrid lipid-mesoporous silica nanoparticles for effective chemo-photothermal therapy of pancreatic cancer

Nanoparticle-based drug delivery systems are designed to reach tumor sites based on their enhanced permeation and retention effects. However, a lack of interaction of these nanoparticles with cancer cells might lead to reduced uptake in the tumors, which might compromise the therapeutic efficacy of the system. Therefore, we developed bortezomib and IR-820-loaded hybrid-lipid mesoporous silica nanoparticles conjugated with the hydrophobic-binding peptide, cyclosporine A (CsA), and referred to them as CLMSN/BIR. Upon reaching the tumor site, CsA interacts hydrophobically with the cancer cell membranes to allow effective uptake of the nanoparticles. Nanoparticles ～160?nm in size were prepared and the stability of IR-820 significantly improved. High cellular uptake of the nanoparticles was evident with pronounced apoptotic effects in PANC-1 and MIA PaCa-2 cells that were mediated by the chemotherapeutic effect of bortezomib and the photothermal and reactive oxygen species generation effects of IR-820. An in vivo biodistribution study indicated there was high accumulation in the tumor with an enhanced photothermal effect in PANC-1 xenograft mouse tumors. Furthermore, enhanced antitumor effects in PANC-1 xenograft tumors were observed with minimal toxicity induction in the organs of mice. Cumulatively, these results indicated the promising effects of CLMSN/BIR for effective chemo-phototherapy of pancreatic cancers.     

Biodegradable PLGA based nanoparticles for sustained regional lymphatic drug delivery

The purpose of this work is to evaluate biodegradable drug carriers with defined size, hydrophobicity, and surface charge density for preferential lymphatic uptake and retention for sustained regional drug delivery. PLGA–PMA:PLA‐PEG (PP) nanoparticles of defined size and relative hydrophobicity were prepared by nanoprecipitation method. These were compared with PS particles of similar sizes and higher hydrophobicity. PLGA–PMA:PLGA‐COOH (PC) particles at 80:20, 50:50, and 20:80 ratios were prepared by nanoprecipitation for the charge study. Particle size and zeta potential were characterized by dynamic light scattering and laser doppler anemometry, respectively. Particles were administered in vivo to rats subcutaneously. Systemic and lymph node uptake was evaluated by marker recovery. Lymphatic uptake and node retention of PP nanoparticles was shown to be inversely related to size. Lymphatic uptake and node retention of PP particles, as compared to PS particles, was shown to be inversely related to hydrophobicity. Lastly, lymphatic uptake and node retention of PC nanoparticles were directly related to the anionic charge on the particles. In vivo lymphatic uptake and retention in a rat model indicates that the 50 nm PP particles are ideal for sustained regional delivery into the lymphatics for prevention/treatment of oligometastases. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2018–2031, 2010     

Co-delivery of docetaxel and bortezomib based on a targeting nanoplatform for enhancing cancer chemotherapy effects

Using facile polydopamine (PDA)-based surface modification and a pH-sensitive catechol-boronate binding mechanism, a novel drug delivery system was designed for the treatment of breast cancer. The system was able to achieve the following goals: active targeting, pH responsiveness, in vivo blood circulation for a prolonged period of time, and dual drug loading. After coating with PDA, the docetaxel (DTX)-loaded star-shaped copolymer cholic acid-poly(lactide-co-glycolide) nanoparticles (CA-PLGA@PDA/NPs) were functionalized with amino-poly(ethylene glycol)-folic acid (NH₂-PEG-FA) and bortezomib (BTZ) to form the targeting composition, DTX-loaded CA-PLGA@PDA-PEG-FA?+?BTZ/NPs. The novel NPs exhibited similar drug release characteristics compared to unfunctionalized CA-PLGA/NPs. Meanwhile, the incorporated NH₂-PEG-FA contributed to active targeting which was illustrated by cellular uptake experiments and biodistribution studies. Moreover, the pH responsive binding between BTZ and PDA was demonstrated to be effective to release BTZ at the tumor acidic environment for synergistic action with DTX. Both in vitro cytotoxicity and in vivo antitumor studies demonstrated that the novel nanoplatform exhibited the most suitable therapeutic effects. Taken together, the versatile PDA modified DTX-loaded CA-PLGA@PDA-PEG-FA?+?BTZ/NPs offered a promising chemotherapeutic strategy for enhancing breast cancer treatment.     

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy

We reported a simple polydopamine (PDA)-based surface modification method to prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in terms of size, size distribution, zeta potential, transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET) surface area and drug loading content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA-PEP had similar release kinetic profiles of DOX. The PDA coating well controlled DOX release and was highly sensitive to pH value. Confocal laser scanning microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest cellular uptake efficiency due to ligand–receptor recognition. The antitumor effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX-loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT-1376 cells, can be used as a potential targeted drug delivery system for bladder cancer therapy.