基于纳米技术的药物递送策略及其在癌症治疗中的应用

药物的有效递送对于疾病治疗至关重要.由于纳米材料独特的尺寸优势和性能,它在药物递送中可以有效地增强治疗药物到靶点的递送效率、最大限度地减少脱靶率.在癌症治疗方面,纳米材料能够通过功能化实现药物靶向运输和肿瘤联合治疗等,对提高癌症治疗效率具有重要的意义.本文总结了体内和体外应用纳米材料和技术进行药物递送的进展以及面临的挑战,有助于深入全面了解纳米材料和技术在药物递送中的应用.

体内自组装多肽纳米材料及其在肿瘤诊疗中的研究进展

多肽纳米药物由于具有易于设计改造、良好的靶向性、生物相容性和较长的血液循环时间等优势,在生物医学与肿瘤诊疗中具有巨大的潜力.近年来,利用肿瘤微环境原位构建多肽纳米材料的策略已被广泛研究,本文综述了多肽纳米材料通过不同的刺激响应(pH、酶和氧化还原等)实现体内自组装,从而对肿瘤的诊断与治疗产生的积极效果.重点阐述了不同的刺激响应型自组装多肽纳米材料的设计合成及其在肿瘤诊疗中的应用,如对于药物递送系统中的药物富集、渗透和内吞等过程的增强作用,同时简单介绍了其在生物成像上的应用,最后对体内自组装多肽纳米材料的未来发展进行了展望.

Pulse electrochemical synaptic transistor for supersensitive and ultrafast biosensors

High sensitivity and fast response are the figures of merit for benchmarking commercial sensors.Due to the advantages of intrinsic signal amplification,bionic ability,and mechanical flexibility,electrochemical transistors(ECTs)have recently gained increasing popularity in constructing various sensors.In the current work,we have proposed a pulse-driven synaptic ECT for supersensitive and ultrafast biosensors.By pulsing the presynaptic input(drain bias,VD)and setting the modulation potential(gate bias)near transconductance intersection(VG,i),the synaptic ECT-based pH sensor can achieve a record high sensitivity up to 124 mV pH^(-1)(almost twice the Nernstian limit,59.2 mV pH^(-1))and an ultrafast response time as low as 8.75 ms(7169 times faster than the potentiostatic sensors,62.73 s).The proposed synaptic sensing strategy can effectively eliminate the transconductance fluctuation issue during the calibration process of the pH sensor and significantly reduce power consumption.Besides,the most sensitive working point at VG,i has been elaborately figured out through a series of detailed mathematical derivations,which is of great significance to provide higher sensitivity with quasi-nonfluctuating amplification capability.The proposed electrochemical synaptic transistor paired with an optimized operating gate offers a new paradigm for standardizing and commercializing high-performance biosensors.

Endogenous formaldehyde responsive fluorescent probe for bioimaging

Formaldehyde(FA),as the simplest endogenous carbonyl molecule,participates in many biosynthesis and metabolism in living organisms,such as nucleotides and adenosine triphosphate(ATP).FA concentrations are sub-millimolar in the normal healthy body,but can rise significantly in a number of disease pathologies.As a result,detecting endogenous FA is critical for illness diagnosis and rehabilitation therapy monitoring.Recent studies have focused on the FA-responsive turn-on fluorescence probe,which has huge promise in the detection and visualization of FA in living cells and organisms,as well as exceptional use in disease diagnosis and therapeutic monitoring.This review summarizes the fluorescence luminescence mechanism and design concepts of FA fluorescent probes,as well as their recent applications in bioimaging and illness diagnostics.Additionally,this article indicates the present dilemma of FA-responsive fluorescent probe,including selectivity,specificity,and detection mode,which may provide references for the development of FA-responsive fluorescent probes.

肿瘤微环境诱导多肽聚合物原位组装行为研究

设计合成了一种pH响应型的多肽聚合物,在中性条件下能够以聚合物单链的形式存在,在肿瘤微环境弱酸的刺激下发生聚集,提升入胞能力,从而实现对肿瘤细胞的高效杀伤.首先,通过迈克尔加成的方法合成了一系列生物相容性较好的β-硫代酸酯聚合物,并利用固相合成方法合成了治疗肽和穿膜肽2种多肽.然后,将治疗肽修饰上一种酸敏感基团,并将2种多肽通过迈克尔加成反应与聚合物共价连接.得到的多肽聚合物能够在中性水溶液中以单链形式稳定存在,而在pH=6.5条件下发生聚集.最后,在细胞层面对多肽聚合物进行研究,发现其在微酸性条件下可以通过内吞作用进入到肿瘤细胞,并具有更高的抗肿瘤能力.

Polymers with tertiary amine groups for drug delivery and bioimaging

Over the past decade, biopolymers have gained great interests especially in biomedicine due to their physical properties and/or chemical structures changes in response to external stimuli in a certain time fiarne or at a specific location. Among them, poly（β-amino ester）s, methacrylate-based block copolymers and polypeptide with tertiary amine groups have been extensively studied and exhibit pH sensitive properties due to the protonation of tertiary amine groups. The pH values in normal organs, tissues, and subcellular compartments are always different from those in pathological tissues. These interesting properties allow their applications in a variety of fields ranging from diagnosis and therapeutics of diseases. Here, we review the recent progress of poly（β-amino ester）s, methacrylate-based block copolymers and polypeptide with tertiary amine groups and their applications in drug delivery and bioimaging.

An ＂In Vivo Self-assembly＂ Strategy for Constructing Superstructures for Biomedical Applications

The interfacing study of biopolymer and supramolecular chemistry enables a better understanding of fundamental biochemical processes and the creating of new high-performance biomaterials. In this review, we introduced an ＂in vivo self-assembly＂ strategy which means in situ construction of functional self-assembled superstructures in specific physiological or pathological conditions in cell, tissue or animal levels that exhibit diverse biomedical effects. By using this strategy, unexpected phenomena and insights, e.g, assembly/aggregation induced retention （AIR） effect have been demonstrated where the self-assembled nanostructures showed extraordinary enhanced accumulation and retention of therapeutics in targeted sites.

Precise Control of Self-assembly in vivo Based on Polymer-Peptide Conjugates

The self-assembled nanomaterials based on peptides,which have not only good biocompatibility and low toxicity but also high stability and performance,are increasingly becoming an important way for cancer treatment.In this review,we highlight the progress of in vivo self-assembled polymer-peptide conjugates(PPCs)and their application,showing the recent advances in the development of“in vivo self-assembly”strategy for cancer treatment.Given the diverse microenvironments of tumor cells,different responsive assembly strategies(enzyme,pH,redox,temperature,etc.)have been developed to precisely control the assembly at different biological levels,realizing enhanced drug delivery and improved anticancer efficacy.

Peptide-Based AIEgens:From Molecular Design,Stimuli Responsiveness to Biomedical Application

Luminogens with aggregation-induced emission(AIEgens)have a wide range of biomedical applications in bioimaging,photodynamic anticancer,antibacterial therapy,and other fields,owing to their unique photophysical properties.The precise structural design and modification of AIE molecules have aroused great interest in the past years.As peptides-AIE hybrid materials,peptide-based AIEgens generally have better solubility,biocompatibility,and lower systemic toxicity.The functional diversity,modularity,and portability of peptides provide more possibilities for the intelligent structure and functional design of AIEgens.This review summarizes the recent research progress of peptide-based AIEgens nanomaterials,from molecular design,stimuli responsiveness to biomedical application,focusing on the advantages of peptides and AIE molecules as conjugates.Finally,a summary of the challenges and opportunities of peptide-based AIEgens nanomaterials for future clinical biomedical applications is presented.