scholarly journals Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xingyu Hou ◽  
Dan Zhong ◽  
Yunkun Li ◽  
Hongli Mao ◽  
Jun Yang ◽  
...  

Abstract Background Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy. Results The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (< 20 nm) nanoparticles, promoting deep penetration and distribution in tumor tissues. Furthermore, MPNs exhibited not only an excellent stable nanostructure for antitumor doxorubicin (DOX) loading, but rapid dissociation of the nanostructure under an intracellular reductive environment. With the capacity of long blood circulation, deep tumor penetration and fast intracellular drug release, the DOX-loaded multi-pocket nanoparticles demonstrated superior antitumor activities against large 4T1 tumor (~ 250 mm3) bearing mice with reduced side effect. Conclusions Our facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy. Graphic Abstract

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Xin Peng ◽  
Kun Chen ◽  
Wanhua Liu ◽  
Xiongfeng Cao ◽  
Mengru Wang ◽  
...  

AbstractTo date, the ability of nanoplatforms to achieve excellent therapeutic responses is hindered by short blood circulation and limited tumor accumulation/penetration. Herein, a soft mesoporous organosilica nanoplatform modified with hyaluronic acid and cyanine 5.5 are prepared, denoted SMONs-HA-Cy5.5, and comparative studies between SMONs-HA-Cy5.5 (24.2 MPa) and stiff counterparts (79.2 MPa) are conducted. Results indicate that, apart from exhibiting a twofold increase in tumor cellular uptake, the soft nanoplatforms also display a remarkable pharmacokinetic advantage, resulting in considerably improved tumor accumulation. Moreover, SMONs-HA-Cy5.5 exhibits a significantly higher tumor penetration, achieving 30-μm deeper tissue permeability in multicellular spheroids relative to the stiff counterparts. Results further reveal that the soft nanoplatforms have an easier extravasation from the tumor vessels, diffuse farther in the dense extracellular matrix, and reach deeper tumor tissues compared to the stiff ones. Specifically, the soft nanoplatforms generate a 16-fold improvement (43 vs. 2.72 μm) in diffusion distance in tumor parenchyma. Based on the significantly improved blood circulation and tumor accumulation/penetration, a soft therapeutic nanoplatform is constructed by loading photosensitizer chlorin e6 in SMONs-HA-Cy5.5. The resulting nanoplatform exhibits considerably higher therapeutic efficacy on tumors compared to the stiff ones.


2021 ◽  
pp. 2102027
Author(s):  
Da‐xia Zhang ◽  
Jiang Du ◽  
Rui Wang ◽  
Jian Luo ◽  
Tong‐fang Jing ◽  
...  

Nanoscale ◽  
2021 ◽  
Author(s):  
Jianqin Yan ◽  
Zhuangzhuang Zhang ◽  
xiaohui Zhan ◽  
Keqi Chen ◽  
Yuji Pu ◽  
...  

mproving the deep penetration of nanoparticles and realizing the combination of chemotherapy and immunotherapy have become a promising strategy for cancer treatment. Herein, nuclear-targeted tetrahedral DNA nanostructure (NLS-TDNs, NT) was...


2021 ◽  
Author(s):  
Yanfen Jiang ◽  
Shuqi Dong ◽  
Guoyang Qin ◽  
Li Liu ◽  
Hanying Zhao

Alkylation of thioether-containing block copolymer simultaneously incorporated sulfoniums and phenylboronic acid moieties. The co-assembly of this cationic polymer and protein generated micelles with an H2O2-and ATP-responsive release profile.


2010 ◽  
Vol 84 (18) ◽  
pp. 9350-9358 ◽  
Author(s):  
Alexis Huet ◽  
James F. Conway ◽  
Lucienne Letellier ◽  
Pascale Boulanger

ABSTRACT The Siphoviridae coliphage T5 differs from other members of this family by the size of its genome (121 kbp) and by its large icosahedral capsid (90 nm), which is organized with T=13 geometry. T5 does not encode a separate scaffolding protein, but its head protein, pb8, contains a 159-residue aminoterminal scaffolding domain (Δ domain) that is the mature capsid. We have deciphered the early events of T5 shell assembly starting from purified pb8 with its Δ domain (pb8p). The self assembly of pb8p is regulated by salt conditions and leads to structures with distinct morphologies. Expanded tubes are formed in the presence of NaCl, whereas Ca2+ promotes the association of pb8p into contracted tubes and procapsids. Procapsids display an angular organization and 20-nm-long internal radial structures identified as the Δ domain. The T5 head maturation protease pb11 specifically cleaves the Δ domain of contracted and expanded tubes. Ca2+ is not required for proteolytic activity but for the organization of the Δ domain. Taken together, these data indicate that pb8p carries all of the information in its primary sequence to assemble in vitro without the requirement of the portal and accessory proteins. Furthermore, Ca2+ plays a key role in introducing the conformational diversity that permits the formation of a stable procapsid. Phage T5 is the first example of a viral capsid consisting of quasi-equivalent hexamers and pentamers whose assembly can be carried out in vitro, starting from the major head protein with its scaffolding domain, and whose endpoint is an icosahedral T=13 particle.


2012 ◽  
Vol 25 (3) ◽  
pp. 422-426 ◽  
Author(s):  
Sanjib Das ◽  
Priyadarshi Ranjan ◽  
Pradipta Sankar Maiti ◽  
Gurvinder Singh ◽  
Gregory Leitus ◽  
...  

RSC Advances ◽  
2017 ◽  
Vol 7 (34) ◽  
pp. 21328-21335 ◽  
Author(s):  
Rujiang Ma ◽  
Chuan Zhang ◽  
Yong Liu ◽  
Chang Li ◽  
Yanling Xu ◽  
...  

Iminoboronate-based dual-responsive micelles were fabricated via simple subcomponent self-assembly for delivery of hydrophilic 1,2-diol-containing drugs.


2002 ◽  
Vol 735 ◽  
Author(s):  
D. Guo ◽  
H. McNally ◽  
M. Pingle ◽  
D. Bergstrom ◽  
R. Bashir

ABSTRACTProtein patterning techniques are crucial for the development of antibody-based biosensor and the study of controlled cell growth. This paper discusses a protein patterning technique based on microelectronic fabrication, DNA hybridization and biotin-streptavidin pair. A gold-on-silicon-dioxide substrate with micron size pattern was fabricated with photolithography and lift-off process. The average surface roughness of the gold pattern is 4.3 nm, measured by contact mode AFM. Thiol derivatized single stranded DNA was attached to the gold pattern surface by the chemical bonding between gold atom and sulfur atom. Surface attached DNA was then hybridized with a biotin conjugated complementary DNA sequence. Thus, the gold pattern was translated into a biotin pattern with similar resolution. Fluorescein conjugated streptavidin was patterned as demonstration. Fluorescence microscopy shows relative uniform streptavidin coverage of micron resolution and low background non-specific binding. The proposed protein patterning technique takes advantage of the high resolution of modern microelectronic fabrication. It has the potential of reaching sub-micron resolution. The biotin-streptavidin pair provides extremely specific and stable linking for protein immobilization. To show its application in biological inspired self-assembly, this technique was used successfully in the self-assembly of 20 nm streptavidin conjugated gold particles.


2020 ◽  
Author(s):  
Sebastian Loescher ◽  
Andreas Walther

<i>Multivalent interactions are an important principle for self-assembly, and have been widely used to assemble colloidal systems. However, binding partners on colloids are typically statistically distributed, which falls short of the possibilities arising from geometrically controlled multivalency patterns as for instance found in viruses. Herein, we use the ultimate precision provided by 3D DNA origamis to introduce colloidal scale multivalency pattern recognition via designing geometrically precise interaction patterns at patches of patchy nanocylinder. This gives rise to self-sorting of colloidal assemblies despite having the same type and number of supramolecular binding motifs – solely based on the pattern located on a 20 x 20 nm cross section. The degree of sorting can be modulated by the geometric overlap of patterns and homo, mixed and alternating supracolloidal polymerizations are demonstrated. We demonstrate that geometric positioning of multivalency patterns provides additional control to organize soft matter, and we believe the concept to be of importance for engineering biological response and to be generalizable for other precision nanoparticles and soft matter objects.</i>


2013 ◽  
Vol 538 ◽  
pp. 181-184 ◽  
Author(s):  
Xin De Tang ◽  
Ye Chen ◽  
Fa Qi Yu ◽  
Mei Shan Pei

Organic/inorganic hybrid materials based upon stimuli-responsive copolymers have attracted an inceasing attention. Compared with the polymeric materials, these hybrid materials can form aggregates in aqueous solution with much more stable shape-persistance due to the inorganic structure, which facilitate the mass delivery and long-term life. A novel hybrid material based on a new reactive block copolymer, poly(ethylene oxide)-block-poly{3-(trimethoxysilyl)propyl methacrylate-co-N-isopropylacrylamide-co-6-[4-(4-methoxyphenylazo)phenoxy]hexyl methacrylate} [PEO-P(TMSPMA-NIPAM-AzoMA)] was synthesized via atom transfer radical polymerization (ATRP). The vesicles were obtained by self-assembly of the resulting block copolymer in a selective solvent, and then the PTMSPMA block was subjected to hydrolysis and polycondensation reaction to fix vesicle wall in the presence of triethylamine as a catalyst. The photo- and thermo- dual-responsive properties of the vesicles were investigated.


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