Gene Vectors Research Articles

Integrity of Newton’s cooling law based on thermal convection theory of heat transfer and entropy transfer

Although thermal convection is omnipresent in nature and technology and serves important purposes in various energy transport systems, whether convection can be viewed as an independent heat transfer means has long been argued The constant coefficient in the original version or convective heat transfer coefficient defined in the modern version of Newton’s cooling law quantifies the ratio of the surface heat flux to the temperature difference between a body surface and an adjacent fluid. However, none of the consistent analytical expressions for these two coefficients are present in Newton’s cooling law. The inherently complex relationship between these pending coefficients and convective heat flux vectors makes revealing the convective mechanism extremely difficult. Theoretical determination of these coefficients would bring new insights to thermal convection and direct applications to thermal management. Here we theoretically show consistent analytical expressions for the constant and convective heat transfer coefficients for various flows to make Newton’s cooling law a complete scientific law. For this purpose, a three-dimensional (3D) energy transfer theory of thermal convection is developed, and the convective heat flux vector, entropy flux vector and entropy generation rate inside the system are derived for both single-phase and phase-change flows. By recasting a control volume system into an equivalent control mass system and employing the first and second laws of thermodynamics, the fundamental advective heat transfer mode characterized by temperature differences and entropy changes is demonstrated. The physical implications underlying the 3D convective formulae are elucidated. Comparisons of the analytical results with laminar experiments and turbulent flow measurement benchmark data validate our theoretical findings. Our 3D heat and entropy transfer theory will broaden the research area of thermal convection processes and open up a new arena for the design and thermal management of convective heat transfer in single-phase and phase-change flows.

Core-Shell Structures from the Coassembly of Lipoprotein-like Nanoparticles and Plasmid DNA for Gene Delivery.

We reported self-assembled core-shell nanoparticles (NPs) based on lipoprotein-like NPs and plasmid DNA (pDNA). Lipoprotein-like NPs were prepared using cholic acid (CA)-modified lipopeptides. We designed six different lipopeptides with different peptide segments to construct a series of NPs. It was proven that these NPs have different positive surface charges. These NPs could bind pDNA through electrostatic interaction to form core-shell complexes. The interactions between NPs and pDNA were systematically investigated. The number of NP charges determines the strength of the interaction between NPs and pDNA. Thus, various types of core-shell structures, such as loose and dense core-shell NPs, were found in this system. Cytotoxicity test confirmed that the carriers had no toxicity. We also proved that the core-shell structures have a good cell transfection effect. This study would expand the application of lipopeptide assemblies in the gene delivery field, which may lead to the development of peptide-based gene vectors for therapeutic application.

Advances in Biomaterial-Mediated Gene Therapy for Articular Cartilage Repair.

Articular cartilage defects caused by various reasons are relatively common in clinical practice, but the lack of efficient therapeutic methods remains a substantial challenge due to limitations in the chondrocytes’ repair abilities. In the search for scientific cartilage repair methods, gene therapy appears to be more effective and promising, especially with acellular biomaterial-assisted procedures. Biomaterial-mediated gene therapy has mainly been divided into non-viral vector and viral vector strategies, where the controlled delivery of gene vectors is contained using biocompatible materials. This review will introduce the common clinical methods of cartilage repair used, the strategies of gene therapy for cartilage injuries, and the latest progress.

Preparation of PEI-modified nanoparticles by dopamine self-polymerization for efficient DNA delivery.

Achieving efficient and safe gene delivery is of greatsignificance to promote the development of gene therapy. In this work, a polydopamine (PDA) layer was coated on the surface of Fe3 O4 nanoparticles (NPs) by dopamine (DA) self-polymerization, and then magnetic Fe3 O4 NPs were prepared by the Michael addition between amino groups in polyethyleneimine (PEI) and PDA. The prepared Fe3 O4 NPs (named Fe3 O4 @PDA@PEI) were characterized by Fourier transform infrared (FTIR), atomic force microscopy (AFM), and scanning electron microscopy (SEM). As an efficient and safe gene carrier, the potential of Fe3 O4 @PDA@PEI was evaluated by agarose gel electrophoresis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, fluorescence microscopy, and flow cytometry. The results show that the Fe3 O4 @PDA@PEI NPs are stable hydrophilic NPs with a particle size of 50-150nm. It can efficiently condense DNA at low N/P ratios and protect it from nuclease degradation. In addition, the Fe3 O4 @PDA@PEI NPs have higher safety than PEI. Further, the Fe3 O4 @PDA@PEI/DNA polyplexes could be effectively absorbed by cells and successfully transfected and exhibit higher cellular uptake and gene transfection efficiency than PEI/DNA polyplexes. The findings indicate that the Fe3 O4 @PDA@PEI NPs have the potential to be developed into a novel gene vector.

Adeno-Associated Virus Gene Therapy for Hemophilia.

In vivo gene therapy is rapidly emerging as a new therapeutic paradigm for monogenic disorders. For almost three decades, hemophilia A (HA) and hemophilia B (HB) have served as model disorders for the development of gene therapy. This effort is soon to bear fruit with completed pivotal adeno-associated viral (AAV) vector gene addition trials reporting encouraging results and regulatory approval widely anticipated in the near future for the current generation of HA and HB AAV vectors. Here we review the clinical development of AAV gene therapy for HA and HB and examine outstanding questions that have recently emerged from AAV clinical trials for hemophilia and other monogenic disorders.

Watershed urbanization enhances the enrichment of pathogenic bacteria and antibiotic resistance genes on microplastics in the water environment

Microplastics (MPs) serve as vectors for microorganisms and antibiotic resistance genes (ARGs) and contribute to the spread of pathogenic bacteria and ARGs across various environments. Patterns of microbial communities and ARGs in the biofilm on the surface of MPs, also termed as plastisphere, have become an issue of global concern. Although antibiotic resistome in the plastisphere has been detected, how watershed urbanization affects patterns of potential pathogens and ARGs in the microplastic biofilms is still unclear. Here, we compared the bacterial communities, the interaction between bacterial taxa, pathogenic bacteria, and ARGs between the plastisphere and their surrounding water, and revealed the extensive influence of urbanization on them. Our results showed that bacterial communities and interactions in the plastisphere differed from those in their surrounding water. Microplastics selectively enriched Bacteroidetes from water. In non-urbanized area, the abundance of Oxyphotobacteria was significantly (p < 0.05) higher in plastisphere than that in water, while α-Proteobacteria was significantly (p < 0.05) higher in plastisphere than those in water of urbanized area. Pathogenic bacteria, ARGs, and mobile genetic elements (MGEs) were significantly (p < 0.05) higher in the urbanized area than those in non-urbanized area. MPs selectively enriched ARG-carrying potential pathogens, i.e., Klebsiella pneumoniae and Enterobacter cloacae, and exhibited a distinct effect on the relative abundance of ARG and pathogens in water with different urbanization levels. We further found ARGs were significantly correlated to MGEs and pathogenic bacteria. These results suggested that MPs would promote the dissemination of ARGs among microbes including pathogenic bacteria, and urbanization would affect the impact of MPs on microbes, pathogens, and ARGs in water. A high level of urbanization could enhance the enrichment of pathogens and ARGs by MPs in aquatic systems and increase microbial risk in aquatic environments. Our findings highlighted the necessity of controlling the spread of ARGs among pathogens and the usage of plastic products in ecosystems of urban areas.

CMIC: predicting DNA methylation inheritance of CpG islands with embedding vectors of variable-length k-mers

BackgroundEpigenetic modifications established in mammalian gametes are largely reprogrammed during early development, however, are partly inherited by the embryo to support its development. In this study, we examine CpG island (CGI) sequences to predict whether a mouse blastocyst CGI inherits oocyte-derived DNA methylation from the maternal genome. Recurrent neural networks (RNNs), including that based on gated recurrent units (GRUs), have recently been employed for variable-length inputs in classification and regression analyses. One advantage of this strategy is the ability of RNNs to automatically learn latent features embedded in inputs by learning their model parameters. However, the available CGI dataset applied for the prediction of oocyte-derived DNA methylation inheritance are not large enough to train the neural networks.ResultsWe propose a GRU-based model called CMIC (CGI Methylation Inheritance Classifier) to augment CGI sequence by converting it into variable-length k-mers, where the length k is randomly selected from the range k_{min } to k_{max }, N times, which were then used as neural network input. N was set to 1000 in the default setting. In addition, we proposed a new embedding vector generator for k-mers called splitDNA2vec. The randomness of this procedure was higher than the previous work, dna2vec.ConclusionsWe found that CMIC can predict the inheritance of oocyte-derived DNA methylation at CGIs in the maternal genome of blastocysts with a high F-measure (0.93). We also show that the F-measure can be improved by increasing the parameter N, that is, the number of sequences of variable-length k-mers derived from a single CGI sequence. This implies the effectiveness of augmenting input data by converting a DNA sequence to N sequences of variable-length k-mers. This approach can be applied to different DNA sequence classification and regression analyses, particularly those involving a small amount of data.

Generating accurate 3D gaze vectors using synchronized eye tracking and motion capture.

Assessing gaze behavior during real-world tasks is difficult; dynamic bodies moving through dynamic worlds make gaze analysis difficult. Current approaches involve laborious coding of pupil positions. In settings where motion capture and mobile eye tracking are used concurrently in naturalistic tasks, it is critical that data collection be simple, efficient, and systematic. One solution is to combine eye tracking with motion capture to generate 3D gaze vectors. When combined with tracked or known object locations, 3D gaze vector generation can be automated. Here we use combined eye and motion capture and explore how linear regression models generate accurate 3D gaze vectors. We compare spatial accuracy of models derived from four short calibration routines across three pupil data inputs: the efficacy of calibration routines was assessed, a validation task requiring short fixations on task-relevant locations, and a naturalistic object interaction task to bridge the gap between laboratory and "in the wild" studies. Further, we generated and compared models using spherical and Cartesian coordinate systems and monocular (left or right) or binocular data. All calibration routines performed similarly, with the best performance (i.e., sub-centimeter errors) coming from the naturalistic task trials when the participant is looking at an object in front of them. We found that spherical coordinate systems generate the most accurate gaze vectors with no differences in accuracy when using monocular or binocular data. Overall, we recommend 1-min calibration routines using binocular pupil data combined with a spherical world coordinate system to produce the highest-quality gaze vectors.

Bioinformatic Analysis of the Genetic Mechanism of Biomineralization of Biogenic Magnetic Nanoparticles in Bacteria Capable of Tumor-Specific Accumulation

Background. Current methods of targeted cancer therapy are not always effective enough and can lead to side effects, such as an increased risk of autoimmune diseases. It is known that some bacteria are capable of specific accumulation in malignant tumors, and therefore can be used as an alternative means of targeted drug delivery. However, the genetic mechanism of tumor-specific accumulation of bacteria is not fully understood and needs to be studied in more detail. Objective. This work aims to identify, by methods of comparative genomics methods, magnetically controlled bacteria among those for which tumor-specific accumulation has already been experimentally shown. Methods. To identify magnetically controlled bacterial strains, i.e., bacteria that biomineralize biogenic magnetic nanoparticles (BMN), the method of comparative genomics was used, namely: pairwise alignment of proteomes with amino acid sequences of Mam-proteins of required for biomineralization of BMN in magneto­tactic bacteria Magnetospirillum gryphiswaldense MSR-1. Sequence alignments were performed in the BLAST program of the US National Center for Biotechnology Information (NCBI). Results. The conducted bioinformatic analysis showed that strains of bacteria in which the ability to accumulate specifically in tumors has been experimentally proven are potential producers of BMN of different types. Among them there are potential producers of intracellular crystalline BMN, potential producers of intracellular amorphous BMN, and extracellular crystalline BMN Conclusions. It is expedient to use bacteria-producing BMN as gene vectors and systems of targeted drug delivery to tumors that biomineralize BMN.

A Fault-Tolerant 24-Sided Voltage Space Vector Structure for Open-End Winding Induction Motor Drive

This article proposes a method of generating 24-sided polygonal voltage space vector structure composed of 24 real active vectors and a zero vector. Each active vector is a real vector in contrast to switched average vectors in literature. Generation of real 24-sided vectors minimizes switching losses and improves quality of phase voltage compared to switched averaged vectors technique. An important feature of the presented scheme is elimination of lower order harmonics up to 19th order from motor phase voltage throughout the modulation range that gives reduction in torque pulsation and near sinusoidal phase current. The proposed scheme extends the linear modulation range till 99.42 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\%$</tex-math></inline-formula> . Open-end winding induction motor is fed with primary and secondary inverters from either ends. Primary and secondary inverters are implemented by cascading two-level inverters. DC sources for both the inverters are realized using a simple star-delta transformer combination. The proposed concepts are verified with laboratory prototype and the respective results during the steady-state, transient, and fault scenario are presented. The supporting loss analysis and harmonic performance of the proposed drive is performed with existing topologies.

Weighted deep factorizing heterogeneous molecular network for genome-phenome association prediction.

Genome-phenome association (GPA) prediction can promote the understanding of biological mechanisms about complex pathology of phenotypes (i.e., traits and diseases). Traditional heterogeneous network-based GPA approaches overwhelmingly need to project heterogeneous data toward homogeneous network for data fusion and prediction, such projections result in the loss of heterogeneous network structure information. Matrix factorization based data fusion can avoid such projection by integrating multi-type data in a coherent way, but they typically perform linear factorization and cannot mine the nonlinear relationships between molecules, which compromise the accuracy of GPA analysis. Furthermore, most of them can not selectively synergy network topology and node attribution information in a principle way. In this paper, we propose a weighted deep matrix factorization based solution (WDGPA) to predict GPAs by selectively and differentially fusing heterogeneous molecular network and diverse attributes of nodes. WDGPA firstly assigns weights to inter/intra-relational data matrices and attribute data matrices, and performs deep matrix factorization on these matrices of heterogeneous network in a cooperative manner to obtain the nonlinear representations of different nodes. In addition, it performs low-rank representation learning on the attribute data with the shared nonlinear representations. In this way, both the network topology and node attributes are jointly mined to explore the representations of molecules and complex interplays between molecules and phenotypes. WDGPA then uses the representational vectors of gene and phenotype nodes to predict GPAs. Experimental results on maize and human datasets confirm that WDGPA outperforms competitive methods by a large margin under different evaluation protocols.

DELIVERY OF ANTI-PD-1 GENE WITH RECOMBINANT ADENO-ASSOCIATED VIRUS (RAAV) AS PREVENTIVE AND CURATIVE THERAPY OF INFECTIOUS DISEASES IN CHILDHOOD : LITERATURE REVIEW

Infections in children are common and are the highest cause of hospitalization in children, especially in children aged 0-4 years. The binding of PD-1 (Programmed Cell Death-1) glycoprotein on its ligand in CD4+ and CD8+ T cells activates a pathway that results in T cell dysfunction. Inserting the anti-PD1 gene into rAAV opens opportunities for preventing and treating infections in children. This literature review aims to determine the potential of anti-PD1 gene rAAV as a new modality for preventing and treating pathogen infections in children. The procedure of searching for literature to answer questions was carried out through online searching of journals in the last ten years. The use of anti-PD-1 has shown to increase the immune response against certain viral, bacterial and parasitic infections. Using rAAV as an anti-PD-1 gene vector has great potential to be a preventive or curative therapy for various infections in children. Further research and development are needed to determine the viral model, dose, indications, and contraindications to the use of the rAAV-transmitted anti-PD-1 gene for the treatment of infectious diseases in children.

Concurrent transposon engineering and CRISPR/Cas9 genome editing of primary CLL-1 chimeric antigen receptor–natural killer cells

BackgroundNatural killer (NK) cell genome editing promises to enhance the innate and alloreactive anti-tumor potential of NK cell adoptive transfer. DNA transposons are versatile non-viral gene vectors now being adapted to primary NK cells, representing important tools for research and clinical product development. Aims and MethodsWe set out to generate donor-derived, primary chimeric antigen receptor (CAR)-NK cells by combining the TcBuster transposon system with Epstein–Barr virus–transformed lymphoblastoid feeder cell-mediated activation and expansion. ResultsThis approach allowed for clinically relevant NK-cell expansion capability and CAR expression, which was further enhanced by immunomagnetic selection based on binding to the CAR target protein.The resulting CAR-NK cells targeting the myeloid associated antigen CLL-1 efficiently targeted CLL-1–positive AML cell lines and primary AML populations, including a population enriched for leukemia stem cells. Subsequently, concurrent delivery of CRISPR/Cas9 cargo was applied to knockout the NK cell cytokine checkpoint cytokine-inducible SH2-containing protein (CIS, product of the CISH gene), resulting in enhanced cytotoxicity and an altered NK cell phenotype. ConclusionsThis report contributes a promising application of transposon engineering to donor-derived NK cells and emphasizes the importance of feeder mediated NK cell activation and expansion to current protocols.

Research on image content description in Chinese based on fusion of image global and local features.

Most image content modelling methods are designed for English description which is different form Chinese in syntax structure. The few existing Chinese image description models do not fully integrate the global features and the local features of an image, limiting the capability of the models to represent the details of the image. In this paper, an encoder-decoder architecture based on the fusion of global and local features is used to describe the Chinese image content. In the encoding stage, the global and local features of the image are extracted by the Convolutional Neural Network (CNN) and the target detection network, and fed to the feature fusion module. In the decoding stage, an image feature attention mechanism is used to calculate the weights of word vectors, and a new gating mechanism is added to the traditional Long Short-Term Memory (LSTM) network to emphasize the fused image features, and the corresponding word vectors. In the description generation stage, the beam search algorithm is used to optimize the word vector generation process. The integration of global and local features of the image is strengthened to allow the model to fully understand the details of the image through the above three stages. The experimental results show that the model improves the quality of Chinese description of image content. Compared with the baseline model, the score of CIDEr evaluation index improves by 20.07%, and other evaluation indices also improve significantly.

Effect of molecular weight of polysaccharide on efficient plasmid DNA delivery by polyethylenimine‐polysaccharide‐Fe(III) complexes

AbstractPolyethylenimine (PEI) is considered as the gold standard for evaluating non‐viral gene vectors due to its proton sponge effect and high transfection efficiency. However, its cytotoxicity limits its application. Rice bran polysaccharide (RBP) is rich in nature and beneficial for preparation of biodegradable biomaterials. In this work, three PEI modified RBP‐Fe complexes (PIP‐1, PIP‐2, and PIP‐3) were prepared based on RBP with different molecular weight (Mw). Then the potential of PIP complexes for plasmid DNA (pDNA) delivery and the influence of Mw was studied. PIP complexes showed better safety and higher gene transfection efficiency than PEI. PIP‐1 was prepared by RBP with lower Mw and could formed PIP‐1/pDNA nanoparticle with lower particle size which exhibited higher gene transfection efficiency than other PIP complexes prepared by RBP with higher Mw. The results indicate that the PIP/pDNA complex exhibits a multi‐pathway cellular uptake mechanism. Clathrin dependent and caveolin dependent endocytosis and macropinocytosis were involved in the cellular uptake process of PIP/pDNA complex. It is hoped that this study can provide useful enlightenment for the research and development of gene vector based on polysaccharide.

Ecotoxicological and health implications of microplastic-associated biofilms: a recent review and prospect for turning the hazards into benefits.

Microplastics (MPs), over the years, have been regarded as a severe environmental nuisance with adverse effects on our ecosystem as well as human health globally. In recent times, microplastics have been reported to support biofouling by genetically diverse organisms resulting in the formation of biofilms. Biofilms, however, could result in changes in the physicochemical properties of microplastics, such as their buoyancy and roughness. Many scholars perceived the microplastic-biofilm association as having more severe consequences, providing evidence of its effects on the environment, aquatic life, and nutrient cycles. Furthermore, other researchers have shown that microplastic-associated biofilms have severe consequences on human health as they serve as vectors of heavy metals, toxic chemicals, and antibiotic resistance genes. Despite what is already known about their adverse effects, other interesting avenues are yet to be fully explored or developed to turn the perceived negative microplastic-biofilm association to our advantage. The major inclusion criteria for relevant literature were that it must focus on microplastic association biofilms, while we excluded papers solely on biofilms or microplastics. A total of 242 scientific records were obtained. More than 90% focused on explaining the environmental and health impacts of microplastic-biofilm association, whereas only very few studies have reported the possibilities and opportunities in turning the microplastic biofilms association into benefits. In summary, this paper concisely reviews the current knowledge of microplastic-associated biofilms and their adverse consequences and further proposes some approaches that can be developed to turn the negative association into positive.

Integrase deficient lentiviral vector: prospects for safe clinical applications.

HIV-1 derived lentiviral vector is an efficient transporter for delivering desired genetic materials into the targeted cells among many viral vectors. Genetic material transduced by lentiviral vector is integrated into the cell genome to introduce new functions, repair defective cell metabolism, and stimulate certain cell functions. Various measures have been administered in different generations of lentiviral vector systems to reduce the vector’s replicating capabilities. Despite numerous demonstrations of an excellent safety profile of integrative lentiviral vectors, the precautionary approach has prompted the development of integrase-deficient versions of these vectors. The generation of integrase-deficient lentiviral vectors by abrogating integrase activity in lentiviral vector systems reduces the rate of transgenes integration into host genomes. With this feature, the integrase-deficient lentiviral vector is advantageous for therapeutic implementation and widens its clinical applications. This short review delineates the biology of HIV-1-erived lentiviral vector, generation of integrase-deficient lentiviral vector, recent studies involving integrase-deficient lentiviral vectors, limitations, and prospects for neoteric clinical use.

Root Hair Apex is the Key Site for Symplastic Delivery of Graphene into Plants.

Uptake kinetics and delivery mechanisms of nanoparticles (NPs) in crop plants need to be urgently understood for the application of nanotechnology in agriculture as delivery systems for eco-friendly nanoagrochemicals. Here, we investigated the uptake kinetics, translocation pathway, and key internalization process of graphene in wheat (Triticum aestivum L.) by applying three specific hydroponic cultivation methods (submerging, hanging, and split-root). Quantification results on the uptake of carbon-14 radiolabeled graphene in each tissue indicated that graphene could enter the root of wheat and further translocate to the shoot with a low delivery rate (<2%). Transmission electron microscopy (TEM) images showed that internalized graphene was transported to adjacent cells through the plasmodesmata, clearly indicating the symplastic pathway of graphene translocation. The key site for the introduction of graphene into root cells for translocation through the symplastic pathway is evidenced to be the apex of growing root hair, where the newly constructed primary cell wall is much thinner. The confirmation of uptake kinetics and delivery mechanisms is useful for the development of nanotechnology in sustainable agriculture, especially for graphene serving as the delivery vector for pesticides, genes, and sensors.

Construction of Alumni Information Analysis Model Based on Big Data

In order to integrate and utilize alumni resources in a better way, big data is utilized to construct alumni information analysis model based on improved hierarchical clustering algorithm, so as to realize mining and retrieval of alumni information. First,the basic principle of hierarchical clustering algorithm is analyzed concretely. Moreover, the improvement is performed on this basis, and a method of calculating the distance between class clusters based on the ant colony optimization is proposed, which uses the shortest distance of the ant colony algorithm to optimally solve the distance between hierarchical class clusters, so as to improve the clustering accuracy. Then, the alumni information analysis model based on improved hierarchical clustering algorithm is constructed, and the model is divided into text preprocessing, keyword extraction, text feature vector generation, name disambiguation, and alumni recognition modules. Finally, the improved hierarchical clustering algorithm and construction of model are verified by experiments. The results show that the accuracy of the improved agglomerative hierarchical clustering algorithm is as high as 86.4% on average and 3.8% and 4.8% more than the two traditional algorithms. Thus, the clustering effect of the algorithm is better, and the proposed alumni analysis model can effectively process text disambiguation of web pages and identification of alumni information, which has certain effectiveness.

Red fluorescent AIEgens based multifunctional nonviral gene vectors for the efficient combination of gene therapy and photodynamic therapy in anti-cancer

Precise molecular engineering of AIEgens-based cationic delivery systems for high transfection efficiency (TE) and effective photodynamic therapy (PDT) holds a huge potential for cancer treatment. Herein, three amphiphiles (DT-C6/8/12-M) consisting of di(triazole-[12]aneN3) (M) and 1,1-dicyano-2-phenyl-2-(4-diphenylamino)phenyl-ethylene (DT) units have been developed to achieve luminescent tracking, efficient TE, and effective PDT in vitro and in vivo. These compounds exhibited strong aggregated induced emission (AIE) at 630 nm and mega Stokes shifts of up to 160 nm. They were able to bind DNA into nanoparticles with suitable sizes, positive surface potential, and good biocompatibility in the presence of DOPE. Among them, vector DT-C12-M/DOPE with n-dodecyl linker achieved a transfection efficiency as high as 42.3 folds that of Lipo2000 in PC-3 cell lines. DT-C12-M/DOPE exhibited the capability of successful endo/lysosomal escape and rapid nuclear delivery of pDNA, and the gene delivery process was clearly monitored via confocal laser scanning microscopy. Moreover, efficient reactive oxygen species (ROS) generation by DT-C12-M upon light irradiation led to effective PDT in vitro . We further show that combination of p53 gene therapy and PDT dramatically enhanced cancer therapeutic outcome in vivo. This “three birds, one stone” strategy offers a novel and promising approach for real-time tracking of gene delivery and better cancer treatment