Amino modified nanofibers anchored to Prussian blue nanoparticles selectively remove Cs+ from water.

To improve the selective separation performance of silica nanofibers (SiO2 NFs) for cesium ions (Cs+) and overcome the defects of Prussian blue nanoparticles (PB NPs), PB/SiO2-NH2 NFs were prepared to remove Cs+ from water. Among them, 3-aminopropyltriethoxysilane (APTES) underwent an alkylation reaction with SiO2, resulting in the formation of a dense Si-O-Si network structure that decorated the surface of SiO2 NFs. Meanwhile, the amino functional groups in APTES combined with Fe3+ and then reacted with Fe2+ to form PB NPs, which anchored firmly on the aminoated SiO2 NFs surface. In our experiment, the maximum adsorption capacity of PB/SiO2-NH2 NFs was 111.38 mg/g, which was 31.5 mg/g higher than that of SiO2 NFs. At the same time, after the fifth cycle, the removal rate of Cs+ by PB/SiO2-NH2 NFs adsorbent was 75.36% ± 3.69%. In addition, the adsorption isotherms and adsorption kinetics of PB/SiO2-NH2 NFs were combined with the Freundlich model and the quasi-two-stage fitting model, respectively. Further mechanism analysis showed that the bond between PB/SiO2-NH2 NFs and Cs+ was mainly a synergistic action of ion exchange, electrostatic adsorption and membrane separation.

Identification of QTNs, QTN-by-environment interactions, and their candidate genes for salt tolerance related traits in soybean.

BACKGROUND: Salt stress significantly reduces soybean yield. To improve salt tolerance in soybean, it is important to mine the genes associated with salt tolerance traits. RESULTS: Salt tolerance traits of 286 soybean accessions were measured four times between 2009 and 2015. The results were associated with 740,754 single nucleotide polymorphisms (SNPs) to identify quantitative trait nucleotides (QTNs) and QTN-by-environment interactions (QEIs) using three-variance-component multi-locus random-SNP-effect mixed linear model (3VmrMLM). As a result, eight salt tolerance genes (GmCHX1, GsPRX9, Gm5PTase8, GmWRKY, GmCHX20a, GmNHX1, GmSK1, and GmLEA2-1) near 179 significant and 79 suggested QTNs and two salt tolerance genes (GmWRKY49 and GmSK1) near 45 significant and 14 suggested QEIs were associated with salt tolerance index traits in previous studies. Six candidate genes and three gene-by-environment interactions (GEIs) were predicted to be associated with these index traits. Analysis of four salt tolerance related traits under control and salt treatments revealed six genes associated with salt tolerance (GmHDA13, GmPHO1, GmERF5, GmNAC06, GmbZIP132, and GmHsp90s) around 166 QEIs were verified in previous studies. Five candidate GEIs were confirmed to be associated with salt stress by at least one haplotype analysis. The elite molecular modules of seven candidate genes with selection signs were extracted from wild soybean, and these genes could be applied to soybean molecular breeding. Two of these genes, Glyma06g04840 and Glyma07g18150, were confirmed by qRT-PCR and are expected to be key players in responding to salt stress. CONCLUSIONS: Around the QTNs and QEIs identified in this study, 16 known genes, 6 candidate genes, and 8 candidate GEIs were found to be associated with soybean salt tolerance, of which Glyma07g18150 was further confirmed by qRT-PCR.

Identification of the domestication gene GmCYP82C4 underlying the major quantitative trait locus for the seed weight in soybean.

KEY MESSAGE: A major quantitative trait locus (QTL) for the hundred-seed weight (HSW) was identified and confirmed in the two distinct soybean populations, and the target gene GmCYP82C4 underlying this locus was identified that significantly associated with soybean seed weight, and it was selected during the soybean domestication and improvement process. Soybean is a major oil crop for human beings and the seed weight is a crucial goal of soybean breeding. However, only a limited number of target genes underlying the quantitative trait loci (QTLs) controlling seed weight in soybean are known so far. In the present study, six loci associated with hundred-seed weight (HSW) were detected in the first population of 573 soybean breeding lines by genome-wide association study (GWAS), and 64 gene models were predicted in these candidate QTL regions. The QTL qHSW_1 exhibits continuous association signals on chromosome four and was also validated by region association study (RAS) in the second soybean population (409 accessions) with wild, landrace, and cultivar soybean accessions. There were seven genes in qHSW_1 candidate region by linkage disequilibrium (LD) block analysis, and only Glyma.04G035500 (GmCYP82C4) showed specifically higher expression in flowers, pods, and seeds, indicating its crucial role in the soybean seed development. Significant differences in HSW trait were detected when the association panels are genotyped by single-nucleotide polymorphisms (SNPs) in putative GmCYP82C4 promoter region. Eight haplotypes were generated by six SNPs in GmCYP82C4 in the second soybean population, and two superior haplotypes (Hap2 and Hap4) of GmCYP82C4 were detected with average HSW of 18.27 g and 18.38 g, respectively. The genetic diversity of GmCYP82C4 was analyzed in the second soybean population, and GmCYP82C4 was most likely selected during the soybean domestication and improvement process, leading to the highest proportion of Hap2 of GmCYP82C4 both in landrace and cultivar subpopulations. The QTLs and GmCYP82C4 identified in this study provide novel genetic resources for soybean seed weight trait, and the GmCYP82C4 could be used for soybean molecular breeding to develop desirable seed weight in the future.

Ultrasound contrast agents from microbubbles to biogenic gas vesicles.

Microbubbles have been the earliest and most widely used ultrasound contrast agents by virtue of their unique features: such as non-toxicity, intravenous injectability, ability to cross the pulmonary capillary bed, and significant enhancement of echo signals for the duration of the examination, resulting in essential preclinical and clinical applications. The use of microbubbles functionalized with targeting ligands to bind to specific targets in the bloodstream has further enabled ultrasound molecular imaging. Nevertheless, it is very challenging to utilize targeted microbubbles for molecular imaging of extravascular targets due to their size. A series of acoustic nanomaterials have been developed for breaking free from this constraint. Especially, biogenic gas vesicles, gas-filled protein nanostructures from microorganisms, were engineered as the first biomolecular ultrasound contrast agents, opening the door for more direct visualization of cellular and molecular function by ultrasound imaging. The ordered protein shell structure and unique gas filling mechanism of biogenic gas vesicles endow them with excellent stability and attractive acoustic responses. What's more, their genetic encodability enables them to act as acoustic reporter genes. This article reviews the upgrading progresses of ultrasound contrast agents from microbubbles to biogenic gas vesicles, and the opportunities and challenges for the commercial and clinical translation of the nascent field of biomolecular ultrasound.

Deep-learning based broadband reflection reduction metasurface.

Reflection reduction metasurface (RRM) has been drawing much attention due to its potential application in stealth technology. However, the traditional RRM is designed mainly based on trial-and-error approaches, which is time-consuming and leads to inefficiency. Here, we report the design of a broadband RRM based on deep-learning methodology. On one hand, we construct a forward prediction network that can forecast the polarization conversion ratio (PCR) of the metasurface in a millisecond, demonstrating a higher efficiency than traditional simulation tools. On the other hand, we construct an inverse network to immediately derive the structure parameters once a target PCR spectrum is given. Thus, an intelligent design methodology of broadband polarization converters has been established. When the polarization conversion units are arranged in chessboard layout with 0/1 form, a broadband RRM is achieved. The experimental results show that the relative bandwidth reaches 116% (reflection<-10 dB) and 107.4% (reflection<-15 dB), which demonstrates a great advantage in bandwidth compared with the previous designs.

Ultrasound-Induced Piezocatalysis Triggered NO Generation for Enhanced Hypoxic Tumor Therapy.

Conventional NO gas generation based on l-arginine (l-Arg) is usually dependent on H2O2 and O2, both of which are very limited within the tumor microenvironment, thus greatly limiting l-Arg's therapeutic effect. Herein, a novel nanoplatform for efficiently triggering NO production based on ultrasound-induced piezocatalysis was developed, which was fabricated by coating amphiphilic poly-l-arginine (DSPE-PEG2000-Arg, DPA) on the piezoelectric material of barium titanate (BTO). The resulting BTO@DPA nanoparticles can efficiently generate H2O2, 1O2, and O2 via ultrasound-induced piezocatalysis based on BTO and oxidize the surface arginine to produce NO, which can even further interact with the reactive oxygen species (ROS) to produce more reactive peroxynitrite, thus inducing serious tumor cell apoptosis both in hypoxia and normoxia. After intravenous injection, BTO@DPA accumulated well at the tumor tissue at 4 h postinjection; later, ultrasound irradiation on the tumor not only achieved the best tumor inhibition rate of ∼70% but also completely inhibited tumor metastasis to the lungs via the alleviation of tumor hypoxia. Such a strategy was not dependent on the tumor microenvironment and can be well controlled by ultrasound irradiation, providing a simple and efficient therapy paradigm for hypoxic tumor.

Identification of major quantitative trait loci and candidate genes for seed weight in soybean.

KEY MESSAGE: Four major quantitative trait loci for 100-seed weight were identified in a soybean RIL population under five environments, and the most likely candidate genes underlying these loci were identified. Seed weight is an important target of soybean breeding. However, the genes underlying the major quantitative trait loci (QTL) controlling seed weight remain largely unknown. In this study, a soybean population of 300 recombinant inbred lines (RILs) derived from a cross between PI595843 (PI) and WH was used to map the QTL and identify candidate genes for seed weight. The RIL population was genotyped through whole genome resequencing, and phenotyped for 100-seed weight under five environments. A total of 38 QTL were detected, and four major QTL, each explained at least 10% of the variation in 100-seed weight, were identified. Six candidate genes within these four major QTL regions were identified by analyses of their tissue expression patterns, gene annotations, and differential gene expression levels in soybean seeds during four developmental stages between two parental lines. Further sequence variation analyses revealed a C to T substitution in the first exon of the Glyma.19G143300, resulting in an amino acid change between PI and WH, and thus leading to a different predicted kinase domain, which might affect its protein function. Glyma.19G143300 is highly expressed in soybean seeds and encodes a leucine-rich repeat receptor-like protein kinase (LRR-RLK). Its predicted protein has typical domains of LRR-RLK family, and phylogenetic analyses reveled its similarity with the known LRR-RLK protein XIAO (LOC_Os04g48760), which is involved in controlling seed size. The major QTL and candidate genes identified in this study provide useful information for molecular breeding of new soybean cultivars with desirable seed weight.

Ultrasmall porphyrin-silica core-shell dots for enhanced fluorescence imaging-guided cancer photodynamic therapy.

Clinically used small-molecular photosensitizers (PSs) for photodynamic therapy (PDT) share similar disadvantages, such as the lack of selectivity towards cancer cells, short blood circulation time, life-threatening phototoxicity, and low physiological solubility. To overcome such limitations, the present study capitalizes on the synthesis of ultra-small hydrophilic porphyrin-based silica nanoparticles (core-shell porphyrin-silica dots; PSDs) to enhance the treatment outcomes of cancer via PDT. These ultra-small PSDs, with a hydrodynamic diameter less than 7 nm, have an excellent aqueous solubility in water (porphyrin; TPPS3-NH2) and enhanced tumor accumulation therefore exhibiting enhanced fluorescence imaging-guided PDT in breast cancer cells. Besides ultra-small size, such PSDs also displayed an excellent biocompatibility and negligible dark cytotoxicity in vitro. Moreover, PSDs were also found to be stable in other physiological solutions as a function of time. The fluorescence imaging of porphyrin revealed a prolonged residence time of PSDs in tumor regions, reduced accumulation in vital organs, and rapid renal clearance upon intravenous injection. The in vivo study further revealed reduced tumor growth in 4T1 tumor-bearing bulb mice after laser irradiation explaining the excellent photodynamic therapeutic efficacy of ultra-small PSDs. Thus, ultrasmall hydrophilic PSDs combined with excellent imaging-guided therapeutic abilities and renal clearance behavior represent a promising platform for cancer imaging and therapy.

Thermal Cloak: Theory, Experiment and Application.

In the past two decades, owing to the development of metamaterials and the theoretical tools of transformation optics and the scattering cancellation method, a plethora of unprecedented functional devices, especially invisibility cloaks, have been experimentally demonstrated in various fields, e.g., electromagnetics, acoustics, and thermodynamics. Since the first thermal cloak was theoretically reported in 2008 and experimentally demonstrated in 2012, great progress has been made in both theory and experiment. In this review, we report the recent advances in thermal cloaks, including the theoretical designs, experimental realizations, and potential applications. The three areas are classified according to the different mechanisms of heat transfer, namely, thermal conduction, thermal convection, and thermal radiation. We also provide an outlook toward the challenges and future directions in this fascinating area.

Cyanine conjugates in cancer theranostics.

Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as well. Alternatively, the covalent conjugation of cyanine with other potent therapeutic agents not only boosts its therapeutic efficacy but also broadens its therapeutic modality. Herein, we summarize miscellaneous cyanine-therapeutic agent conjugates in cancer theranostics from literature published between 2014 and 2020. The application scenarios of such theranostic cyanine conjugates covered common cancer therapeutic modalities, including chemotherapy, phototherapy and targeted therapy. Besides, cyanine conjugates that serve as nanocarriers for drug delivery are introduced as well. In an additional section, we analyze the potential of these conjugates for clinical translation. Overall, this review is aimed to stimulate research interest in exploring unattempted therapeutic agents and novel conjugation strategies and hopefully, accelerate clinical translation in this field.

Cyanine Conjugate-Based Biomedical Imaging Probes.

Cyanine is a class of fluorescent dye with meritorious fluorescence properties and has motivated numerous researchers to explore its imaging capabilities by miscellaneous structural modification and functionalization strategies. The covalent conjugation with other functional molecules represents a distinctive design strategy and has shown immense potential in both basic and clinical research. This review article summarizes recent achievements in cyanine conjugate-based probes for biomedical imaging. Particular attention is paid to the conjugation with targeting warheads and other contrast agents for targeted fluorescence imaging and multimodal imaging, respectively. Additionally, their clinical potential in cancer diagnostics is highlighted and some concurrent impediments for clinical translation are discussed.

Fibronectin-targeted dual-acting micelles for combination therapy of metastatic breast cancer.

Stage IV breast cancer, which has a high risk of invasion, often develops into metastases in distant organs, especially in the lung, and this could threaten the lives of women. Thus, the development of more advanced therapeutics that can efficiently target metastatic foci is crucial. In this study, we built an dual-acting therapeutic strategy using micelles with high stability functionalized with fibronectin-targeting CREKA peptides encapsulating two slightly soluble chemotherapy agents in water, doxorubicin (D) and vinorelbine (V), which we termed C-DVM. We found that small C-DVM micelles could efficiently codeliver drugs into 4T1 cells and disrupt microtubule structures. C-DVM also exhibited a powerful ability to eradicate and inhibit invasion of 4T1 cells. Moreover, an in vivo pharmacokinetics study showed that C-DVM increased the drug circulation half-life and led to increased enrichment of drugs in lung metastatic foci after 24 h. Moreover, dual-acting C-DVM treatment led to 90% inhibition of metastatic foci development and reduced invasion of metastases. C-DVM could potentially be used as a targeted treatment for metastasis and represents a new approach with higher therapeutic efficacy than conventional chemotherapy for stage IV breast cancer that could be used in the future.

Harnessing platelets as functional vectors for contrast enhanced ultrasound imaging and fluorescence imaging.

The recent progress in the development of highly biocompatible nanoplatforms mostly encompasses the use of biological excipients such as red blood cells, cancer cell membranes, and also platelets. Such specialized vectors, if mimicked correctly, have intrinsic ability to navigate through the biological system and perform their intended action without eliciting any cascade of inflammatory processes. Naturally, platelets have been found to accumulate in the wound sites and also interact with circulating tumor cells (CTCs). Inspired by the targeting ability of platelets and the clinical success of ultrasound, herein we developed a novel ultrasound contrast agent (UCA) by backfilling of an insoluble gas into the platelets after lyophilization ex vivo. The as-prepared platelet-based ultrasound contrast agent (P-UCA) disguised the structural integrity of the natural platelets with an average diameter of 3.1 ± 0.4 µm, and could enhance the ultrasound signal both in vitro and in vivo. Besides, we further evaluated that such platelet particles could facilitate active loading of ICG molecules for prolonged in vivo fluorescence imaging compared to the free ICG. Taking all the results together, we established that biological structures such as platelets could be repurposed ex vivo as a"shell" to encapsulate gas and be further extended to load ICG for real-time ultrasound and fluorescence imaging respectively. This not only indicates many potential uses of these MBs in the diagnosis of platelet-related diseases, such as vascular damage, thrombosis, and atherosclerosis, but also serves as a powerful platform with multimodal theranostic capability after active loading of a variety of therapeutic and diagnostic agents.

Amphiphilic Drug Conjugates as Nanomedicines for Combined Cancer Therapy.

Chemotherapy suffers from some limitations such as poor bioavailability, rapid clearance from blood, poor cellular uptake, low tumor accumulation, severe side effects on healthy tissues and most importantly multidrug resistance (MDR) in cancer cells. Nowadays, a series of smart drug delivery system (DDS) based on amphiphilic drug conjugates (ADCs) has been developed to solve these issues, including polymer-drug conjugate (PDC), phospholipid-mimicking prodrugs, peptide-drug conjugates (PepDCs), pure nanodrug (PND), amphiphilic drug-drug conjugate (ADDC), and Janus drug-drug conjugate (JDDC). These ADCs can self-assemble into nanoparticles (NPs) or microbubbles (MBs) for targeted drug delivery by minimizing the net amount of excipients, realizing great goals, such as stealth behavior and physical integrity, high drug loading content, no premature leakage, long blood circulation time, fixed drug combination, and controlled drug-release kinetics. Besides, these self-assembled systems can be further used to load additional therapeutic agents and imaging contrast agents for combined therapy, personalized monitoring of in vivo tumor targeting, and the pharmacokinetics of drugs for predicting the therapeutic outcome. In this review, we will summarize the latest progress in the development of ADCs based combination chemotherapy and discuss the important roles for overcoming the tumor MDR.

Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer.

To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS). Cationic porphyrin microbubbles (CpMBs) were firstly fabricated from a porphyrin grafted lipid with two cationic amino groups (PGL-NH2) and fluorocarbon inert gas of C3F8. Porphyrin group in the CpMBs monolayer could be used as a photosensitizer for PDT, while amino groups could adsorb siRNA through electrostatic interaction for FOXA1 KD, which could inhibit the proliferation of estrogen-dependent ER+ BC. This system showed high photosensitizer and gene loading content. Moreover, CpMBs/siRNA can be converted into nanoparticles with low-frequency pulsed ultrasound (LFUS) exposure, which increase the transfection efficiency of siRNA (∼4 fold) and the porphyrin uptake (∼8 fold) in MCF-7 (a human breast cancer cell line, ER+) by sonoporation effect. In vivo, UTMD was performed under the guidance of CEUS, and the fluorescence intensity of CpMBs/siRNA at the tumour site reached a peak value at 6 h after injection and it was retained in the following 24 h. Furthermore, there was no tumour recurrence during the observation period (21 days) in the group of PDT combined with FXOA1 KD. Compared to the PDT or FOXA1 KD alone group, the combination of these two methods was much more efficient in inhibiting ER+ breast cancer, showing a good synergistic effect. CpMBs/siRNA combined with UTMD dramatically increased the local accumulation of porphyrin and siRNA through ultrasound-induced sonoporation effect under the guidance of CEUS, showing excellent therapeutic effect for estrogen-dependent ER+ breast cancer.

Liposomal Nanotechnology for Cancer Theranostics.

Liposomes are a type of biomimetic nanoparticles generated from self-assembling concentric lipid bilayer enclosing an aqueous core domain. They have been attractive nanocarriers for the delivery of many drugs (e.g. radiopharmaceuticals, chemotherapeutic agents, porphyrin) and diagnostic agents (e.g. fluorescent dyes, quantum dots, Gadolinium complex and Fe3O4) by encapsulating (or adsorbing) hydrophilic one inside the liposomal aqueous core domain (or on the bilayer membrane surface), and by entrapping hydrophobic one within the liposomal bilayer. Additionally, the liposome surface can be easily conjugated with targeting molecules. Liposomes may accumulate in cancerous tissues not only passively via enhanced permeability and retention (EPR) effect, but also actively by targeting cancer cell or angiogenic marker specifically. The multimodality imaging functionalization of liposomal therapeutic agents makes them highly attractive for individualized monitoring of the in vivo cancer targeting and pharmacokinetics of liposomes loading therapeutic drugs, and predicting therapeutic efficacy in combination with the helpful information from each imaging technique. The present review article will highlight some main advances of cancer theranostic liposomes with a view to activate further research in the nanomedicine community.

CuInS2/ZnS Quantum Dots Conjugating Gd(III) Chelates for Near-Infrared Fluorescence and Magnetic Resonance Bimodal Imaging.

A bimodal contrast nanoagent was developed by chelating gadolinium ions to 2-[bis[2-[carboxymethyl-[2-oxo-2-(2-sulfanylethyl-amino)ethyl]amino]ethyl]amino]acetic acid (DTDTPA)-modified CuInS2/ZnS quantum dots (QDs). The longitudinal relaxivity (r1) of the resulted QDs@DTDTPA-Gd nanoparticles (NPs) was calculated to be 9.91 mM-1 s-1, which was 2.5 times as high as that of clinically approved Gd-DTPA (3.9 mM-1 s-1). In addition, the in vivo imaging experiments showed that QDs@DTDTPA-Gd NPs could enhance both near-infrared fluorescence and T1-weighted magnetic resonance (MR) imaging of tumor tissue through passive targeting accumulation. Moreover, the high colloidal and fluorescence stabilities and good biocompatibility indicate that QDs@DTDTPA-Gd NPs have a great potential for use as an efficient nanoagent to integrate the extremely high sensitivity of fluorescence imaging to the high resolution of MR imaging. Integration of bimodal detectability in the same agent of QDs@DTDTPA-Gd NPs can avoid extra stress on the blood clearance mechanisms as the administration of multiple dose of agents.

Near-infrared light-activatable polymeric nanoformulations for combined therapy and imaging of cancer.

Near infrared (NIR) light allows deep tissue penetration and high spatial resolution due to the reduced scattering of long-wavelength photons. NIR light-activatable polymer nanoparticles are widely exploited for enhanced cancer imaging (diagnosis) and therapy owing to their superior photostability, photothermal conversion efficiency (or high emission rate), and minimal toxicity to cells and tissues. This review surveys the most recent advances in the synthesis of different NIR-absorbing and emissive polymer nanoformulations, and their applications for cancer imaging, photothermal therapy, theranostics and combination therapy by delivering multiple small molecule chemotherapeutics. Photo-responsive drug delivery systems for NIR light-triggered drug release are also discussed with particular emphasis on their molecular designs and formulations as well as photo-reaction mechanisms. Finally, outlook and challenges are presented regarding potential clinical applications of NIR light-activatable nanoformulations.

Hyaluronic Acid Conjugated Magnetic Prussian Blue@Quantum Dot Nanoparticles for Cancer Theranostics.

A multifunctional nanotheranostic agent was developed by conjugating both hyaluronic acid and bovine serum albumin coated CuInS2-ZnS quantum dots onto the surface of magnetic Prussian blue nanoparticles. The obtained nanoagent could serve as an efficient contrast agent to simultaneously enhance near infrared (NIR) fluorescence and magnetic resonance (MR) imaging greatly. The coexistence of magnetic core and CD44 ligand hyaluronic acid was found to largely improve the specific uptake of the nanoagent by CD44 overexpressed HeLa cells upon applying an external magnetic field. Both NIR fluorescence and MR imaging in vivo proved high accumulation of the nanoagent at tumor site due to its excellent CD44 receptor/magnetic dual targeting capability. After intravenous injection of the nanoagent and treatment of external magnetic field, the tumor in nude mice was efficiently ablated upon NIR laser irradiation and the tumor growth inhibition was more than 89.95%. Such nanotheranostic agent is of crucial importance for accurately identifying the size and location of the tumor before therapy, monitoring the photothermal treatment procedure in real-time during therapy, assessing the effectiveness after therapy.

Chitosan Functionalized CuS Nanoparticles Boots Gene Transfection via Photothermal Effect.

BACKGROUND: The lack of smart and controllable gene vectors with high safety and efficiency is still a main obstruction for clinical applications of gene therapy. Recently, the external physical stimuli, such as near infrared light induced temperature elevation, have been applied to enhance the gene transfection efficiency and specificity. The aim of this paper is to fabricate chitosan functionalized CuS nanoparticles (CuS@CS NPs) with small size and higher biocompatibility for enhanced gene delivery by photothermal effect. METHODS: CuS@CS NPs were successfully prepared by simple hydrothermal method. The biocompatibility was detected by MTT method and hymolytic analysis. pEGFP-C1was used as gene model, and its expression efficiency was detected by fluorescence microscopy and flow cytometry to investigate the effect of photothermal effect on the transfection efficiency. RESULTS: The CuS@CS NPs around 15 nm were successfully engineered. The modification of CuS nanoparticles with chitosan conduced to higher physiological stability and biocompatibility. The utilization of CuS@CS NPs in combination with external near infrared (NIR) laser irradiation could enhance gene transfection efficiency due to photothermal effect. The gene transfection efficiency of CuS@CS NPs found to increase from 5.05±0.54% (0 min) to 23.47±1.27% (10 min), significantly higher than the free polyethylenimine (18.15±1.03%). CONCLUSION: CuS@CS NPs showed great capability to control gene delivery by an external NIR laser irradiation and enhance the gene transfection efficiency and specificity because of convenient preparation, stabilized optical properties, excellent photothermal effect and good biocompatibility. It encourages further exploration of the CuS@CS NPs as a photocontrollable nanovector for combined photothermal and gene therapy, as well as image guided therapy.