查找使用阿拉丁产品的科研文献

Self-assembled thioether-bridged paclitaxel-dihydroartemisinin prodrug for amplified antitumor efficacy-based cancer ferroptotic-chemotherapy

Yifei Zheng,Chao Qin,Fei Li,Jingxin Qi,Xinyu Chu,Hao Li,Ting Shi,Zhen Yan,Lei Yang,Xiaofei Xin,Lisha Liu,Xiaopeng Han,Lifang Yin

Ferroptosis has been proposed as one form of iron-dependent cell death, overgeneration of high-toxicity hydroxyl radicals (˙OH) tumor sites via Fenton reactions induced cell membrane damage. However, the insufficient intracellular concentrations of both iron and H2O2 limited the anticancer performance of ferroptosis. In this study, ROS-sensitive prodrug nanoassemblies composed of a PEG2000-ferrous compound and a single thioether bond bridged dihydroartemisinin-paclitaxel prodrug were constructed, which fully tapped ex/endogenous iron, ferroptosis inducers, and chemotherapeutic agents. Following cellular uptake, the intracellular oxidizing environment accelerated the self-destruction of nanoassemblies and triggered drug release. In addition to the chemotherapeutic effect, the activated dihydroartemisinin was capable of acting as a toxic ˙OH amplifier via the reinforced Fenton reaction, simultaneously depleting intracellular GSH, as well as inducing glutathione peroxidase 4 inactivation, further enhancing ferroptosis-dependent cancer cell proliferation inhibition. Meanwhile, the ROS generation-inductive and cell cycle arrest effect from the paclitaxel augmented synergetic ferroptotic-chemotherapy of cancer. Thus, the prodrug integrating dihydroartemisinin with paclitaxel via a single thioether bond represents a potent nanoplatform to exert amplified ferroptotic-chemotherapy for improved anticancer efficacy.

pH-responsive PLGA/gelatin porous microspheres containing paclitaxel used for inhibition of cancer cell proliferation

Fenglin Huang,Sisi Yang,Hao Wang,Peiwen Zhao,Bo Zhou,Bo Cheng,Siyan Dong,Jing Yang,Binbin Li,Xinyu Wang

Multi-functional drug-loaded microsphere system can overcome drug resistance and selectively transport drugs to tumor tissues, thus reducing the toxicity to normal tissues, and can achieve long-term effect through drug release, thus becoming a new way to treat tumor-related diseases. Poly (lactic-co-glycolic acid) PLGA/gelatin composite microspheres were prepared by an emulsion solvent evaporation technique. The microsphere shows that it has positive charge and pH response, which is more suitable for the weak acid environment of tumor and has certain targeting effect. At the same time, the scanning electron microscope showed that the surface was loose and rough, and the internal structure was porous, and the morphology was novel. In addition, UV spectrophotometer was used to test the drug loading rate and encapsulation efficiency of the microspheres. For smooth PLGA and PLGA/gelatin microspheres, the latter has better drug loading rate of 11.66% and encapsulation rate of 89.22%. The results showed that among pure paclitaxel , PLGA and PLGA/gelatin microspheres, the latter had the better than performance in the lethal rate of lung cancer cells and could achieve the goal of continuous lethal. Therefore, the preparation of porous drug-loaded microspheres in this study is pH responsive, and can achieve the goal of safe, targeted and efficient inhibition of cancer cell proliferation , and inspire the follow-up anti-cancer research.

Synthesis and anti-cancer evaluation of folic acid-peptide- paclitaxel conjugates for addressing drug resistance

Yuxuan Dai,Xingguang Cai,Xinzhou Bi,Chunxia Liu,Na Yue,Ying Zhu,Jiaqi Zhou,Mian Fu,Wenlong Huang,Hai Qian

The drug resistance and the poor water solubility are major limitations of paclitaxel (PTX) of based chemotherapy. To conquer the two problems, targeting folate (FA) receptor PTX-lytic peptides conjugates were synthesized and evaluated. Compared with PTX, FA-P3-PTX and FA-P7-PTX displayed significantly enhanced cell toxicity in many cancer cells, particularly drug resistant cancer cells MCF-7/PTX. FA-P7-PTX possessed stronger effect on cell toxicity (IC 50  = 2.92 ± 0.2 μM), membrane disrupting activity and pro-apoptosis in MCF-7/PTX cells than FA-P3-PTX. Further investigation displayed that the anti-cancer mechanisms of FA-P3-PTX and FA-P7-PTX might be a mitochondrial impairment and caspase-3-dependent apoptotic cell death . Furthermore, the in vivo antitumor efficacy study confirmed that FA-P7-PTX performed more stronger potency in inhibition of tumors growth than PTX. The study demonstrated that conjugate FA-P7-PTX with superior properties for antineoplastic activity , which makes it a promising potential candidate for drug-resistant cancer therapy.

Optimizing Paclitaxel Oral Absorption and Bioavailability: TPGS Co-Coating via Supercritical Anti-Solvent Fluidized Bed Technology

Zicheng Zhong,Yanling Lan,Jinxing Chen,Lu Ping,Xuchun Li,Qing Wang,Xiaodong Zhuang,Zhenwen Qiu,Tianhui Yuan,Qiupin Guo,Long Xi,Qingguo Li,Dandong Luo

Supercritical anti-solvent fluidized bed (SAS-FB) coating technology has the advantages of reducing particle size, preventing high surface energy particle aggregation, improving the dissolution performance and bioavailability of insoluble drugs. The poor solubility of Biopharmaceutics Classification System (BCS) class IV drugs poses challenges in achieving optimal bioavailability. Numerous anti-cancer drugs including paclitaxel (PTX) belong to the BCS class IV, hindering their therapeutic efficacy. To address this concern, our study explored SAS-FB technology to coat PTX with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) onto lactose. Under our optimized conditions, we achieved a PTX coating efficiency of 96.8%. Further characterization confirmed the crystalline state of PTX in the lactose surface coating by scanning electron microscopy and X-ray powder diffraction. Dissolution studies indicated that SAS-FB processed samples release over 95% of the drug within 1 min. Moreover, cell transmembrane transport assays demonstrated that SAS-FB processed PTX samples co-coated with TPGS had an enhanced PTX internalization into cells and a higher permeability coefficient compared to those without TPGS. Finally, compared to unprocessed PTX, SAS-FB (TPGS) and SAS-FB processed samples showed a 2.66- and 1.49-fold increase in oral bioavailability in vivo, respectively. Our study highlights the efficacy of SAS-FB co-coating for PTX and TPGS as a promising strategy to overcome bioavailability challenges inherent in BCS class IV drugs. Our approach holds broader implications for enhancing the performance of similarly classified medications.

Cu(II)-based complex loaded with drug paclitaxel hydrogels against thyroid cancer and optimizing novel derivatives

Wang Hui-Hui,Yin He-Liang,Yin Wei-Wei,Song Yong-Li,Chen Hong

This study introduces a novel approach for synthesizing a Cu(II)-based coordination polymer (CP), {[Cu(L)(4,4´-OBA)]·H 2 O}n ( 1 ), using a mixed ligand method. The CP was successfully prepared by reacting Cu(NO 3 ) 2 ·3H 2 O with the ligand 3,6-bis(benzimidazol-1-yl)pyridazine in the presence of 4,4´-H 2 OBA, demonstrating an innovative synthesis strategy. Furthermore, a novel hydrogel composed of hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) with a porous structure was developed for drug delivery purposes. This hydrogel facilitates the encapsulation of CP 1 , and enables the loading of paclitaxel onto the composite to form HA/CMCS-CP 1 @paclitaxel. In vitro cell experiments demonstrated the promising modulation of thyroid cancer biomarker genes S100A6 and ARID1A by HA/CMCS-CP 1 @paclitaxel. Finally, reinforcement learning simulations were employed to optimize novel metal–organic frameworks, underscoring the innovative contributions of this study.

Construction of glutathione-responsive paclitaxel prodrug nanoparticles for image-guided targeted delivery and breast cancer therapy

Weiwei Ma,Qiufeng Zhao,Shilong Zhu,Xinyue Wang,Chuangchuang Zhang,Daming Ma,Na Li,Yanyan Yin

Paclitaxel (PTX) remains an essential drug in the treatment of breast cancer. To improve metabolic stability and real-time monitoring of drug location, we develop a visualized nano-prodrug. Novel hyaluronic acid (HA)-coated glutathione (GSH)-sensitive chitosan (CS)-based nano-prodrug (HA/TPE-CS-SS-PTX NPs) with aggregation-induced emission effects (AIE) were accomplished. The prodrug NPs (drug loading 29.32%, particle size 105 nm, regular sphericity) exhibit excellent fluorescence stability. The prodrug NPs could target tumor cells with high expression of CD44 and decompose in the presence of high concentrations of glutathione. In vitro evaluations revealed that the prodrug NPs have significant cytotoxicity on 4T1 cells, and due to their excellent AIE characteristics, their position in cells can be tracked. Moreover, the prodrug NPs also shown superior anti-tumor effects in vivo experimental. Overall, the HA/TPE-CS-SS-PTX NPs we constructed have excellent bio-imaging capabilities and can be served as a potential nanomedicine for PTX delivery against breast cancer.

Biomimetic nanocrystals co-deliver paclitaxel and small-molecule LF3 for ferroptosis-combined chemotherapy for gastric cancer

Qianqian Zhao,Ting Wu,Chunming Tang,Jie Li,Min Wu,Jie Wu,Zhiji Wang,Yinxin Zhu,Huae Xu,Xiaolin Li

Combination chemotherapy is considered more effective than monotherapy in enhancing clinical outcomes. Ferroptosis, a unique form of regulated cell death, has been demonstrated to inhibit tumor growth and progression. Consequently, combining ferroptosis with chemotherapy represents a promising and innovative approach to antitumor therapy. In this study, we developed a novel TMTP1-modified biomimetic nanocrystal (TRNC@P + L) for the co-delivery of PTX and LF3, aiming to achieve ferroptosis-combined chemotherapy in gastric cancer. TRNC@P + L, which incorporates a tumor-homing peptide-modified red blood cell membrane, demonstrated efficient tumor targeting, prolonged circulation, enhanced drug bioavailability, and reduced non-specific toxicities of free PTX and LF3. By utilizing the synergistic effects of PTX and LF3, TRNC@P + L combination therapy significantly inhibited tumor growth, as demonstrated by both in vitro and in vivo studies. Mechanistically, TRNC@P + L triggers ferroptosis in tumor cells by downregulating GPX4 expression, the promotion of ROS accumulation, and the enhancement of lipid peroxidation. These processes synergistically enhance the anticancer efficacy of PTX.

Dendritic Polylysine with Paclitaxel and Triptolide Codelivery for Enhanced Cancer Ferroptosis through the Accumulation of ROS

Yuanyuan Wen,Kaiming Li,Mengnan Ni,Hui Jiang,Haisi Wu,Qinqi Yu,Jinyu Li,Xiaolin Li,Jifu Wei,Wei Wu,Huae Xu

Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8+ T cells and IFN-γ+ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.

Simultaneous determination of free and total paclitaxel in blood in a three-phase laminar flow microchip

Qidan Cai,Huaidong Peng,Jiang Meng,Youshao Yan,Yu Zeng,Paul C.H. Li,Yue Sun

In this study, a three-phase laminar flow microfluidic chip (TPL chip) combined with HPLC was developed for monitoring free and total concentrations of paclitaxel (PTX) in blood simultaneously. A diluted whole blood sample (aqueous phase) was introduced into the chip, ethyl acetate (organic phase) was introduced into the chip for extraction, and an interphase was used to prevent the blood sample from coming into direct contact with the organic phase. Because only free drug can quantitatively diffuse into the organic extraction phase and the free drug fraction has a linear relationship with the dilution factor of blood, both the free and total drug concentrations can be obtained by detecting the concentration of paclitaxel in the organic extraction phase. The governing factor such as flow rate for extraction was optimized. Docetaxel was used as an internal standard. The reliability of the quantitative diffusion of molecules in the TPL chip was proved by the methodological investigation of PTX in PBS sample, which showed a good linearity in the concentration range of 0.5 - 100 µg/mL and a detection limit of 7 ng/mL. Good repeatibilities for retention time (RSD of PTX is 1.23%, docetaxel is 1.14%, n  = 5) and peak area ratio of PTX to docetaxel (RSD is 4.38%) were obtained. For blood sample analysis, only 100 µL of sample was needed and whole pretreatment was finished in 35 min, and a recovery of 94~117% were obtained. The provided method showed advantages in fast analysis speed, minimum sample handing, and potential ability of automation, and integration.

Examining and Delivery and Retention of a Paclitaxel Nano-Drug in Oral Squamous Cell Carcinoma Tissues

Mou Fengping,Xiao Li,Xu Yuanqin

This study aims to investigate the therapeutic effect of a paclitaxel-loaded nano-drug (PTX-mPEGPLA) on oral squamous cell carcinoma (OSCC). PTX-mPEG-PLA nanoparticle (NP) was prepared by loading paclitaxel into the mPEG-PLA nanoparticle and purified by a thin-film hydration method. C57BL/6 mice were used to establish a murine OSCC model. The mice were treated with saline control (G1), paclitaxel (G2), or PTX-mPEG-PLA NPs (G3). After 4 weeks of differential treatment, the saliva of mice in the G1, G2, and G3 groups was collected to detect the concentration of protein markers of OSCC. Also, venous blood and cancer tissues of mice in the three groups were collected for drug concentration measurements. The paclitaxel concentration and retention in G3 mice were significantly higher and more prolonged than those in G2 mice, respectively (P < 0.05). Compared to the level of OSCC protein markers in the saliva of mice in G1 and G2 that in G3 was the lowest. PTX-mPEG-PLA NPs demonstrates effective targeting in the treatment of oral squamous cell carcinoma in mice. It can deliver the drug to the cancerous tissues, increase the drug retention in the same tissues, and effectively inhibit the proliferation and metastasis of malignant tumors.

Formulation and Stability Evaluation of Structure-Altered Paclitaxel Nanosuspensions Stabilized by a Biocompatible Amino Acid Copolymer

Li Mengmeng,Chen Yongchao,Yin Li,Wang Haiyan,Cao Yanping,Wei Zhihao,Wang Yanfei,Yuan Qi,Pu Xiaohui,Zong Lanlan,Duan Shaofeng

To manufacture a stable paclitaxel nanosuspension (PTX-CP-Nanos), poly(L-phenyl-alanine)-b-poly(L-aspartic acid) (PPA-PAA), a multifunctional stabilizer, was synthesized via NCA-based ring-opening copolymerization. PTX-CP-Nanos were manufactured by a microprecipitation-high pressure homogenization method. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) results indicated that the PTX in PTX-CP-Nanos existed in amorphous state. Particle size and zeta potential of the PTX-CP-Nanos were 226.8 ± 2.1 nm and –28.4 ± 0.1 mV, respectively, as indicated by dynamic light scattering method. Transmission electron microscopy (TEM) revealed that the morphology of PTX-CP-Nanos were of rod-like crystals. In addition, it was found that the structure of PTX-CP-Nanos altered to micelles by TEM during dissolution. The dissolution rate of PTX-CP-Nanos was significantly increased compared with the crude crystals but obviously lower than PTX injection, which could be ascribed to the particle size reduction of PTX nanoparticles and the conversion of PTX-CP-Nanos into micelles in the later stage of the dissolution test. The tests of storage stability, dilution stability and plasma stability both showed that PTX-CP-Nanos were significantly more stable than PTX-Nanos stabilized by other traditional surfactants and polymers. The acute toxicity tests demonstrated that PTX-CP-Nanos also had a high systemic safety.

Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

Pengkai Ma,Xuemei Zhang,Ling Ni,Jinming Li,Fengpu Zhang,Zheng Wang,Shengnan Lian,Kaoxiang Sun