Acidity-responsive shell-sheddable camptothecin-based nanofibers for carrier-free cancer drug delivery

Nanoscale ◽  
2019 ◽  
Vol 11 (34) ◽  
pp. 15907-15916 ◽  
Author(s):  
Zhuha Zhou ◽  
Ying Piao ◽  
Lingqiao Hao ◽  
Guanyu Wang ◽  
Zhuxian Zhou ◽  
...  

pH-responsive nanofibers are obtained by the self-assembly of the camptothecin prodrug and surface-coating, which can efficiently enter cancer cells in vitro and penetrate deep into tumor tissue in vivo.

AIChE Journal ◽  
2008 ◽  
Vol 54 (11) ◽  
pp. 2979-2989 ◽  
Author(s):  
Youqing Shen ◽  
Yihong Zhan ◽  
Jianbin Tang ◽  
Peisheng Xu ◽  
Patrick A. Johnson ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-23 ◽  
Author(s):  
Vincent Roy ◽  
Brice Magne ◽  
Maude Vaillancourt-Audet ◽  
Mathieu Blais ◽  
Stéphane Chabaud ◽  
...  

Cancer research has considerably progressed with the improvement of in vitro study models, helping to understand the key role of the tumor microenvironment in cancer development and progression. Over the last few years, complex 3D human cell culture systems have gained much popularity over in vivo models, as they accurately mimic the tumor microenvironment and allow high-throughput drug screening. Of particular interest, in vitrohuman 3D tissue constructs, produced by the self-assembly method of tissue engineering, have been successfully used to model the tumor microenvironment and now represent a very promising approach to further develop diverse cancer models. In this review, we describe the importance of the tumor microenvironment and present the existing in vitro cancer models generated through the self-assembly method of tissue engineering. Lastly, we highlight the relevance of this approach to mimic various and complex tumors, including basal cell carcinoma, cutaneous neurofibroma, skin melanoma, bladder cancer, and uveal melanoma.


2006 ◽  
Vol 12 (4) ◽  
pp. 513-523 ◽  
Author(s):  
Albert D. G. de Roos

Current theories about the origin of the eukaryotic cell all assume that during evolution a prokaryotic cell acquired a nucleus. Here, it is shown that a scenario in which the nucleus acquired a plasma membrane is inherently less complex because existing interfaces remain intact during evolution. Using this scenario, the evolution to the first eukaryotic cell can be modeled in three steps, based on the self-assembly of cellular membranes by lipid-protein interactions. First, the inclusion of chromosomes in a nuclear membrane is mediated by interactions between laminar proteins and lipid vesicles. Second, the formation of a primitive endoplasmic reticulum, or exomembrane, is induced by the expression of intrinsic membrane proteins. Third, a plasma membrane is formed by fusion of exomembrane vesicles on the cytoskeletal protein scaffold. All three self-assembly processes occur both in vivo and in vitro. This new model provides a gradual Darwinistic evolutionary model of the origins of the eukaryotic cell and suggests an inherent ability of an ancestral, primitive genome to induce its own inclusion in a membrane.


1992 ◽  
Vol 3 (1) ◽  
pp. 29-47 ◽  
Author(s):  
G Barnes ◽  
K A Louie ◽  
D Botstein

Conditions were established for the self-assembly of milligram amounts of purified Saccharomyces cerevisiae tubulin. Microtubules assembled with pure yeast tubulin were not stabilized by taxol; hybrid microtubules containing substoichiometric amounts of bovine tubulin were stabilized. Yeast microtubule-associated proteins (MAPs) were identified on affinity matrices made from hybrid and all-bovine microtubules. About 25 yeast MAPs were isolated. The amino-terminal sequences of several of these were determined: three were known metabolic enzymes, two were GTP-binding proteins (including the product of the SAR1 gene), and three were novel proteins not found in sequence databases. Affinity-purified antisera were generated against synthetic peptides corresponding to two of the apparently novel proteins (38 and 50 kDa). Immunofluorescence microscopy showed that both these proteins colocalize with intra- and extranuclear microtubules in vivo.


2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Liya Li ◽  
Wangxiao He ◽  
Weiming You ◽  
Jin Yan ◽  
Wenjia Liu

Abstract Background Clinical translation of therapeutic nuclear acid, particularly those targeting tumor progression, has been hampered by the intrinsic weaknesses of nuclear acid therapeutic including poor systemic stability, rapid clearance, low membrane permeability and lack of targeting ability. Small nuclear acid engineered into carrier-free nanodrugs with structural stability and disease targeting may be viable to overcome pharmaceutical obstacles of nuclear acid. Methods A general method through a mild and simple chemistry was established to convert therapeutic miRNA into an infinite Auric-sulfhydryl coordination supramolecular miRNA termed IacsRNA with near-spherical nanostructure, high colloid as well as anti-hydrolysis stability and low macrophage uptakes. Results IacsRNA presented the increased half-life period in circulation and accumulation at tumor sites in comparison to normal miRNA. Moreover, Iacs-miR-30c showed no toxicity of viscera and sanguis system in the 5-time injection dosage of the treatment. More importantly, Iacs-miR-30c potently suppressed the Wnt signaling pathway in vitro and in vivo, and effectively sensitized both potency of 5-Fu in PDX model of colon cancer and Anti-PD1 in B16F10 homograft model of melanoma. Conclusion Collectively, this work amply confirmed the design of IacsRNA as a general and viable strategy of nano-pharmaceutic to concert flimsy therapeutic miRNA into potential drugs. Considering from a broader perspective, the miRNA-initiated infinite coordination self-assembly strategy has distinct advantages in resurrecting nuclear acid therapeutics, probably bringing new inspiration to RNA-derived therapeutics of a great variety of human diseases including cancer. Graphical Abstract


2020 ◽  
Author(s):  
Ruoning Wang ◽  
Yujie Yang ◽  
Mengmeng Yang ◽  
Dandan Yuan ◽  
Jinyu Huang ◽  
...  

Abstract Background: The treatment of metastatic cancer continues to be very challenging worldwide. Notably, excipient-free nanodispersions that are entirely composed of pharmaceutically active molecules are regarded as promising candidates for the next generation of drug formulations. These molecules are mainly formulated from the self-assembly of drug molecules that enable the safe and effective delivery of therapeutic drugs to local diseased lesions. Herein, we developed a novel and green approach for preparing nanoparticles via the self-assembly of rhein (RHE) and doxorubicin (DOX) molecules, named RHE/DOX nanoparticles (RD NPs); this assembly was associated with π−π stacking interactions and did not involve any organic solvents. Results:Molecular dynamics (MD) simulations showed that DOX molecules tend to assemble around RHE molecules through intermolecular forces. With the advantage of nanosizing, RD NPs improved the intracellular drug retention of DOX. As a dual-drug-loaded nanoformulation, the toxicity of RD NPs to tumor cells in vitro was synergistically enhanced. The combination of DOX and RHE in nanoparticles exhibited a synergistic effect with a combination index (CI) value of 0.51 and showed a stronger ability to induce cell apoptosis compared to that of free DOX. Furthermore, RD NPs treatment not only effectively suppressed primary tumor growth but also successfully inhibited tumor metastasis both in vitro and in vivo, with a good safety profile. Conclusion: The generation of pure nanodrugs via a self-assembly approach might be an option and may provide inspiration for the fabrication of new excipient-free nanodispersions, especially for two small molecular antitumor drugs that could potentially have synergistic antiproliferation effects against metastatic breast cancer.


2020 ◽  
Vol 21 (3) ◽  
pp. 1129 ◽  
Author(s):  
Siddhartha Banerjee ◽  
Mohtadin Hashemi ◽  
Karen Zagorski ◽  
Yuri L. Lyubchenko

The self-assembly of amyloid β (Aβ) proteins into oligomers is the major pathogenic event leading to Alzheimer’s disease (AD). Typical in vitro experiments require high protein concentrations, whereas the physiological concentration of Aβ is in the picomolar to low nanomolar range. This complicates the translation of results obtained in vitro to understanding the aggregation process in vivo. Here, we demonstrate that Aβ42 self-assembles into aggregates on membrane bilayers at low nanomolar concentrations - a pathway in which the membrane plays the role of a catalyst. Additionally, physiological ionic conditions (150 mM NaCl) significantly enhance on-membrane aggregation, leading to the rapid formation of oligomers. The self-assembly process is reversible, so assembled aggregates can dissociate from the membrane surface into the bulk solution to further participate in the aggregation process. Molecular dynamics simulations demonstrate that the transient membrane-Aβ interaction dramatically changes the protein conformation, facilitating the assembly of dimers. The results indicate peptide–membrane interaction is the critical step towards oligomer formation at physiologically low protein concentrations.


2020 ◽  
Vol 142 (23) ◽  
pp. 10383-10399
Author(s):  
Xue-Quan Zhou ◽  
Ming Xiao ◽  
Vadde Ramu ◽  
Jonathan Hilgendorf ◽  
Xuezhao Li ◽  
...  
Keyword(s):  
The Self ◽  

2018 ◽  
Vol 8 (6) ◽  
pp. 272-274
Author(s):  
Hao Wu

A review of cytotoxicity associated with cancer treatments as presented in literature was discussed. In all the studies, the research is aware of the cytotoxic effects of the cancer drug and the delivery form such as nanotechnology-based delivery. The scope of the review was limited to showing 1) the need for modulating cytotoxicity and 2) how cytotoxicity has been controlled in actual studies on treatment plans in vivo and in vitro. Keywords: Cytotoxicity, in vivo, in vitro, nanotechnology, nanoparticles, apoptosis


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