Co-delivery Of siRNA Research Articles

Chitosan based pH-responsive polymeric prodrug vector for enhanced tumor targeted co-delivery of doxorubicin and siRNA

The co-delivery of chemotherapeutic drugs and siRNA has gained increasing attentions owing to the enhanced antitumor efficacy over single administration. In this work, a chitosan-based pH-responsive prodrug vector was developed for the co-delivery of doxorubicin (DOX) and Bcl-2 siRNA. The accumulation of fabricated nanoparticles in hepatoma cells was enhanced by glycyrrhetinic acid receptor-mediated endocytosis. The cumulative release amount of the encapsulated DOX and siRNA reached 90.2 % and 81.3 % in 10 h, respectively. More strikingly, this nanoplatform can efficiently integrate gene- and chemo-therapies with a dramatically enhanced tumor inhibitory rate (88.0 %) in vivo. This co-delivery system may provide the latest strategy to meet the needs of combination therapies for tumors, offering safe and efficient improvements to the synergistic antitumor efficacy of gene-chemotherapies.

Co-delivery of IKBKE siRNA and cabazitaxel by hybrid nanocomplex inhibits invasiveness and growth of triple-negative breast cancer.

IKBKE is an oncogene in triple-negative breast cancer (TNBC), and we demonstrate that IKBKE small interfering RNA (siRNA) inhibits the proliferation, migration, and invasion of TNBC cells. Despite the recent success of siRNA therapeutics targeting to the liver, there still remains a great challenge to deliver siRNAs to solid tumors. Here, we report a hybrid nanocomplex to co-deliver the IKBKE siRNA and cabazitaxel to TNBC to achieve an optimal antitumor effect. The nanocomplex is modified with hyaluronic acid to target CD44 on TNBC cells. The nanocomplex shows higher cellular uptake and better tumor penetration of the encapsulated cargos. The nanocomplex also exhibits high tumor accumulation and antitumor activity in an orthotopic TNBC mouse model. Encapsulation of cabazitaxel in the nanocomplex enhances the activity of the IKBKE siRNA. The hybrid nanocomplex provides a novel and versatile platform for combination therapies using siRNAs and chemotherapy.

M2-Like Tumor-Associated Macrophage-Targeted Codelivery of STAT6 Inhibitor and IKKβ siRNA Induces M2-to-M1 Repolarization for Cancer Immunotherapy with Low Immune Side Effects.

Tumor-associated macrophages (TAMs) usually display the tumor-promoting M2 phenotype rather than the tumoricidal M1 phenotype. Thus, M2-to-M1 repolarization of TAMs has emerged as a promising strategy for tumor immunotherapy nowadays. However, immune side effects remain a great challenge, because phenotypic conversion of macrophages into the proinflammatory M1 phenotype may also be induced in normal tissue. Here, aiming at repolarizing TAMs without altering the M1/M2 polarization balance in healthy organs, we develop a micellar nanodrug with M2-targeting peptides (M2peptide) hidden in the pH-sheddable PEG corona so that an active targeting of M2-like macrophages is triggered only in the acidic tumor microenvironment (TME). The smart nanodrug effectively functions M2-to-M1 repolarization via M2-targeted codelivery of IKKβ siRNA and STAT6 inhibitor AS1517499 (AS), which suppresses the tumor growth and metastasis. Moreover, immune side effects are reduced because the neutral-pH environment in healthy organs does not trigger a “stealth-to-nonstealth” conversion of the nanodrug essential for M2-targeted drug delivery.

Co-delivery of gemcitabine prodrug along with anti NF-κB siRNA by tri-layer micelles can increase cytotoxicity, uptake and accumulation of the system in the cancers.

Combination treatment based on gene and chemotherapy is a promising strategy for effective cancer treatment due to the limited therapeutic efficacy of anticancer drugs. Dual functional polymeric micelles (PMs) have been emerged as potent nanocarriers for combinational cancer therapy. In the present study, the potential of tri-layer PMs loaded with anti-nuclear factor-κB (NF-κB) siRNA and 4-(N)-stearoyl gemcitabine (GemC18) has been investigated for cancer treatment. PMs with different core hydrophobicity were prepared by using poly(ε-caprolactone), polyethyleneimine and polyethylene glycol (PCL-PEI-PEG) copolymers and evaluated. The results revealed that GemC18-loaded PMs were significantly more cytotoxic than free drug on breast and pancreatic cancer cells. However, the cytotoxicity of drug loaded micelles was decreased by increasing the micellar core hydrophobicity because of decreasing drug release rate. Moreover, siRNA loaded PMs could considerably inhibit NF-κB expression. PMs loaded with both GemC18 and siRNA exhibited higher capability to induce apoptosis and inhibit migration of both cells. PMs with the most hydrophobic core indicated higher tumor accumulation efficiency via in-vivo imaging study. In conclusion, the prepared PMs hold a promise as an attractive dual functional delivery system for an effective cancer therapy.

Nanoparticle-based co-delivery of siRNA and paclitaxel for dual-targeting of glioblastoma.

Aim: To explore the therapeutic effect of nanoparticle-based dual-targeting delivery of antitumor agents for glioblastoma treatment. Materials & methods: A hepatitis B core protein-virus-like particle (VLP)-based dual-targeting delivery system was designed with the primary brain targeting peptide TGN for blood-brain barrier penetration and tumor vascular preferred ligand RGD (arginine-glycine-aspartic acid) for glioblastoma targeting. Chemo- and gene-therapeutic agents of paclitaxel and siRNA were co-packaged inside the vehicle. Results: The results demonstrated efficient delivery of the packaged agents to invasive tumor sites. The combination of chemo- and gene-therapies demonstrated synergistic antitumor effects through enhancing necrosis and apoptosis, as well as being able to inhibit tumor invasion with minimal cytotoxicity. Conclusion: Our hepatitis B core-VLP-based dual-targeting delivery of chemo- and gene-therapeutic agents possesses a synergistic antitumor effect for glioblastoma therapy.

Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy.

SummaryIn some malignant tumor, especially for pancreatic tumor, poor solid-tumor penetration of nanotherapeutics impedes their treatment efficacy. Herein, we develop a polymer-peptide conjugate with the deep tissue penetration ability, which undergoes a cascade process under ultrasound (US), including (1) the singlet oxygen 1O2 is generated by P18, (2) the thioketal bond is cleaved by the 1O2, (3) the departure of PEG chains leads to the in situ self-assembly, and (4) the resultant self-assembled PK nanoparticles show considerable cellular internalization. Owing to the synergistic effect of US on increasing the membrane permeability, the endocytosis and lysosome escape of PK nanoparticles are further enhanced effectively, resulting in the improved therapeutic efficacy. Thanks to the high tissue-penetrating depth and spatial precision of US, PTPK presents enhanced tumor inhibition in an orthotopic pancreatic tumor model. Therefore, the US-activated cascade effect offers a novel perspective for precision medicine and disease theranostics.

Application of mesoporous silica nanoparticles for drug delivery to cancer cells

Cancer is one of the main causes of death worldwide. Chemotherapy is the most common method for cancer therapy which represent non-specific side effects on normal cells and tissues and drug resistance in cancer cells. There are two main mechanisms for Multi Drug Resistance (MDR) in cancer cells including: drug efflux pump and activation of anti-apoptotic pathways. Cancer chemotherapy disadvantages can be overcome by using nanoparticulate drug delivery systems like Mesoporous Silica Nanoparticles (MSNs) that have been used as drug delivery system since 2001. The present review included synthesis, targeted (active or passive) drug delivery to cancer cells, co-delivery of anticancer drugs and siRNA by MSNs and its toxicity. This review revealed that MSNs are good candidate for drug delivery to cancer cells due to its unique properties including: controllable pore and particle sizes, thermal and chemical stability, modifications of outer and inner surfaces of nanoparticles for drug and siRNA loading, attachment of ligand for targeted drug delivery, high drug loading capacity and controlled drug release, biocompatibility and biodegradation in aqueous medium.

Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel (PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid (FA) and glucose (Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCo-polyethyleneimine (FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol (PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu (NPsB) and FeCo-PEI-PLA-PEG-FA/Glu (NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX. Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

Ultrasound-Mediated Long-Circulating Nanopolymer Delivery of Therapeutic siRNA and Antisense MicroRNAs Leads to Enhanced Paclitaxel Sensitivity in Epithelial Ovarian Cancer Chemotherapy.

Epithelial ovarian cancer (EOC) is one of the leading malignant tumors that seriously threaten women's health. The development of new drugs or increasing the sensitivities of current chemotherapy drugs is critically needed. The purpose of this study was to assess the synergistic effects of two silencing RNAs [salt-inducible kinase 2 (SIK2) siRNA and antisense-microRNA21 (anti-miR21)] encapsulated in long-circulating folate-lipid-poly(lactic-co-glycolic acid) (PLGA) hybrid nanopolymers (FaLPHNPs) administered using an ultrasound- and microbubble (US-MB)-mediated approach to sensitize human EOC xenografts to paclitaxel (PTX). In the in vitro assays, this lipid-PLGA hybrid nanopolymer exhibited an extended circulation profile (t1/2: ∼8.5 h); US-MB-mediated complementary delivery of FaLPHNPs resulted in a significant reduction in EOC cell (OVCR3, A2780, and SKOV3) proliferation. In vivo, there was a 2.5-fold increase (p < 0.05) in RNA delivery in EOC xenografts, which resulted in a notable inhibition of tumor growth compared with that in the non-ultrasound-mediated and PTX alone-treated controls. We validated the therapeutic roles of SIK2, the target gene in treating advanced ovarian cancer, and anti-miR21 by evaluating the significant inhibition of tumor growth upon SIK2 silencing and inhibition of endogenous miR21 function. In summary, the results of this study revealed that US-MB-mediated codelivery of SIK2 siRNA, and anti-miR21 encapsulated in a folate-lipid-PLGA hybrid polymer nanoparticle could significantly improve the sensitivity of EOC tumors to PTX and is a highly effective approach for treating EOC in complementary experiments. Further research of this strategy could lead to better treatment results for patients with EOC.

Co-delivery of AKT3 siRNA and PTEN Plasmid by Antioxidant Nanoliposomes for Enhanced Antiproliferation of Prostate Cancer Cells.

Globally, prostate cancer is the fifth major cancer type and the second leading cause of cancer-related death in men. In 2018, about 1.3 million prostate cancer cases were reported worldwide. It is reported that loss of PTEN (tumor suppressor gene) expression leads to hyperactivation of the PI3K/AKT pathway and thus induces uncontrolled cell proliferation. Loss or mutation in regular PTEN expression is reported to occur in ∼30% of primary prostate cancer cases and ∼65% of metastatic cancer cases. Restoring the PTEN expression could inhibit the PI3K/AKT/mTOR signaling pathway, thus avoid the growth of prostate cancer cells. In this work, we have synthesized a multifunctional nanoliposomal formulation incorporating PTEN plasmid, AKT3 siRNA, and antioxidant cerium oxide nanoparticles (CeNPs). The nanoliposomes were able to successfully internalize in prostate cancer (PC-3) cells, restore the expression of PTEN protein, and knock down AKT3 mRNA. Further, the multifunctional nanoliposomes induce DNA damage and apoptosis in prostate cancer cells. The investigation of the PI3K/AKT/mTOR signaling pathway revealed that PTEN protein and apoptosis-specific proteins are overexpressed, leading to the inhibition of oncoproteins and, thus, prostate cancer.

Monoclonal Antibody 2C5-Modified Mixed Dendrimer Micelles for Tumor-Targeted Codelivery of Chemotherapeutics and siRNA.

Targeted delivery of chemotherapeutics to tumors has the potential to reach a high dose at the tumor while minimizing systemic exposure. Incorporation of antibody within a micellar platform represents a drug delivery system for tumor-targeted delivery of antitumor agents. Such modified immunomicelles can result in an increased accumulation of antitumor agents and enhanced cytotoxicity toward cancer cells. Here, mixed dendrimer micelles (MDM) composed of PEG2k-DOPE-conjugated generation 4 polyamidoamine dendrimer G4-PAMAM-PEG2k-DOPE and PEG5k-DOPE were coloaded with doxorubicin and siMDR-1. This formulation was further modified with monoclonal antibodies 2C5 with nucleosome-restricted specificity that effectively recognized cancer cells via the cell-surface-bound nucleosomes. Micelles with attached 2C5 antibodies significantly enhanced cellular association and tumor killing in both monolayer and spheroid tumor models as well as in vivo in experimental animals compared to the nontargeted formulations.

Codelivery of STAT3 siRNA and BV6 by carboxymethyl dextran trimethyl chitosan nanoparticles suppresses cancer cell progression.

High expression of inhibitor of apoptosis (IAP) molecules in cancer cells promotes cancer cell chemoresistance. Use of BV6, a well-known IAP inhibitor, along with inhibition of signal transducer and activator of transcription 3 (STAT3), which is an important factor in the survival of tumor cells, and NIK as a mediator of BV6 unpredicted side effects, can induce effective apoptosis in tumor cells. The present study has investigated the combination therapy of cancer cells using Carboxymethyl Dextran-conjugated trimethyl chitosan (TMC-CMD) nanoparticles (NPs) loaded with NIK/STAT3-specific siRNA and BV6 to synergistically induce apoptosis in the breast, colorectal and melanoma cancer cell lines. Our results showed that in addition to enhanced pro-apoptotic effects, this combination therapy reduced proliferation, cell migration, colony formation, and angiogenesis, along with expression of factors including IL-10 and HIF in tumor cells. The results indicate the potential of this combination therapy for further investigation in animal models of cancer.

Nanocarrier Mediated siRNA Delivery Targeting Stem Cell Differentiation.

Stem cell-based regenerative medicine holds exceptional therapeutic potential and hence the development of efficient techniques to enhance control over the rate of differentiation has been the focus of active research. One of the strategies to achieve this involves delivering siRNA into stem cells and exploiting the RNA interference (RNAi) mechanism. Transport of siRNA across the cell membrane is a challenge due to its anionic property, especially in primary human cells and stem cells. Moreover, naked siRNA incites immune responses, may cause off-target effects, exhibits low stability and is easily degraded by endonucleases in the bloodstream. Although siRNA delivery using viral vectors and electroporation has been used in stem cells, these methods demonstrate low transfection efficiency, cytotoxicity, immunogenicity, events of integration and may involve laborious customization. With the advent of nanotechnology, nanocarriers which act as novel gene delivery vehicles designed to overcome the problems associated with safety and practicality are being developed. The various nanomaterials that are currently being explored and discussed in this review include liposomes, carbon nanotubes, quantum dots, protein and peptide nanocarriers, magnetic nanoparticles, polymeric nanoparticles, etc. These nanodelivery agents exhibit advantages such as low immunogenic response, biocompatibility, design flexibility allowing for surface modification and functionalization, and control over the surface topography for achieving the desired rate of siRNA delivery and improved gene knockdown efficiency. This review also includes discussion on siRNA co-delivery with imaging agents, plasmid DNA, drugs etc. to achieve combined diagnostic and enhanced therapeutic functionality, both for in vitro and in vivo applications.

Novel Chitosan Derivatives with Reversible Cationization and Hydrophobicization for Tumor Cytoplasm-Specific Burst Co-delivery of siRNA and Chemotherapeutics.

Despite the great potential of combination therapy based on siRNA and chemotherapeutics, an efficient vehicle with abilities of well drug co-loading, synchronizing in vivo trafficking, and target-specific co-burst release remains elusive, which results in a suboptimal synergistic potency. Herein, a novel chitosan amphiphile (PEI-ss-HECS-ss-OA, HSPO) with glutathione (GSH)-reversible cationization and hydrophobicization by polyethylenimine (PEI) and octylamine (OA), respectively, was developed for this purpose. HSPO spontaneously assembled in aqueous solution to be a micellar system and effectively co-encapsulated the two drugs with an adjustable dosage ratio. With a surface charge inversion strategy by hyaluronic acid (HA) coating, the HA(HSPO) co-delivery micelles with a negative surface charge (-21.45 ± 1.44 mV) and suitable size (192.52 ± 7.41 nm) selectively accumulated into CD44 overexpressed A549 tumors through a combination of passive and active targeting mechanism. Then, tumor cytoplasm-selective co-burst release was obtained through GSH triggered collapse of the amphiphilic assembly alongside a decrease of positive charge condensation, finally leading to an enhanced synergistic antitumor effect with a superior inhibition ratio of 86.63%. Overall, this study validated the great promise of HSPO as an efficient site-specific rapid co-trafficking vehicle of siRNA and chemotherapeutics for a remarkable synergistic tumor inhibition.

Stimuli-responsive combination therapy of cisplatin and Nrf2 siRNA for improving antitumor treatment of osteosarcoma

Cisplatin is a widely applied therapeutics for the treatment of osteosarcoma. However, its clinical applications have been hindered due to low efficacy and bioavailability, and particularly frequent emergence of reactive oxygen species (ROS)-decrease induced drug resistance. The transcription factor NF-E2-related factor 2 (Nrf2) is increased in cancer patients and induces poor outcome in osteosarcoma treatment, making it a novel target to improve the efficacy of chemotherapy. Herein, a hyaluronidase-responsive multi-layer liposome (HLCN) for co-delivery of cisplatin and Nrf2 siRNA (siNrf2) is developed. It is composed of Vpr52-96 modified liposome covered with hyaluronic acid (HA). HLCN selectively accumulates in osteosarcoma by targeting tumor-specific CD44, and can be degraded by endosomal hyaluronidase to generate cationic liposome, which promotes the endosomal escape of Vpr52-96, cisplatin and siNrf2. HLCN can effectively decrease Nrf2 level, promote ROS generation, activate itochondrial apoptotic pathway, and consequently enhance anticancer efficacy of cisplatin. Particularly, HLCN shows high cytotoxicity to osteosarcoma cells with an IC50 value of about 1 µM, which is four-fold lower than liposomal cisplatin (IC50 4 µM), indicating that Nrf2 silence can significantly improve cisplatin sensitivity in cancer cells. Importantly, HLCN can remarkably inhibit tumor growth in the xenograft osteosarcoma mice with minimal systemic adverse effects. Therefore, this novel stimuli-responsive combination therapy of cisplatin and siNrf2 provides a promising strategy for the treatment of osteosarcoma.

Polymeric micelle with pH-induced variable size and doxorubicin and siRNA co-delivery for synergistic cancer therapy

Cancer is one of the most fatal diseases which imposes a serious threat to human health worldwide. Combination therapy of gene drugs with chemotherapeutic drugs is a strategy to improve anticancer effect. In this study, a triblock copolymer was synthesized to enable the codelivery of siRNA and DOX for combination therapy. With a pH-sensitive core, a cationic intermediate layer, and a stable PEG shell, the system can not only load nucleic acid drugs and chemotherapeutic drugs, but also achieve the effect of pH-sensitive drug release. In vitro experiments indicated that the size of micelles could be changed at different pH values, and DOX could be released rapidly at low pH values, which is good for killing cancer cells. And in vivo experiments proved that polymer vector loaded with siRNA and DOX can be enriched in tumor tissues, and release their loads rapidly when they get into tumor. Consequently, the polymeric micelles have a great potential to co-deliver chemotherapeutic drugs and gene drugs to cancer tissues for combination therapy.

Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy

Immunotherapy has exhibited great potential in cancer treatment. However, for immunosuppressive tumors such as pancreatic cancer, immunotherapy is far from satisfactory. PI3K-γ and colony stimulating factor-1/colony stimulating factor-1 receptor (CSF-1/CSF-1R) pathways are involved in the infiltration and polarization of immunosuppressive cells including M2 tumor associated macrophages (M2 TAMs), causing a suppressive tumor immune microenvironment (TIME) in pancreatic cancer. Herein, a M2 TAM targeting nanomicelle was developed to co-deliver PI3K-γ inhibitor NVP-BEZ 235 and CSF-1R-siRNA for specific TAMs reprogramming and antitumor immune responses activation. M2 TAM targeting peptide M2pep was modified on a mixed micelle, which was potent to co-encapsulate BEZ 235 and CSF-1R siRNA. The formulated nanomicelle increased M2 TAM targeting efficiency both in vitro and in vivo. Compared with single pathway blockade, dual blockade of PI3k-γ and CSF-1R demonstrated enhanced TAM remodeling effects by reducing M2 TAM level and elevating M1 TAM level, and also suppressed tumor infiltration of myeloid-derived suppressor cells (MDSCs). Consequently, the M2 TAM targeting reprogramming system activated antitumor immune responses and achieved enhanced anti-pancreatic tumor effects via PI3K-γ blockade and downregulation of CSF-1R. The M2pep modified nanomicelle provides a promising method for co-delivery of siRNA and small molecule inhibitor to M2 TAM. Dual inhibition of both PI3K-γ and CSF-1R can remodel TIME and activate antitumor immune responses synergistically, providing an alternative approach for pancreatic cancer treatment.

Co-delivery of p38α MAPK and p65 siRNA by novel liposomal glomerulus-targeting nano carriers for effective immunoglobulin a nephropathy treatment

Glomerulonephritis related renal failure is a frequent cause of end-stage renal disease, and immunoglobulin A nephropathy (IgAN) is the most frequent type of primary glomerulonephritis. As damage induced by IgAN mostly attributes to inflammation responses, inhibiting inflammation in glomerulus can protect normal renal function and delay the onset of renal failure. Hence, reducing levels of p38 MAPK and p65 which are essential regulators in p38 MAPK and NF-κB related inflammation responses could be effective against IgAN. Here, we rationally designed and constructed size- and surface charge- dependent glomerulus-targeting liposomal nanoparticles which are loaded with both p38α MAPK and p65 siRNA. Experiments show that our nanoparticles successfully crossed fenestrated endothelium, accumulated in mesangial cells and endothelial cells, efficiently silenced p38α MAPK and p65 genes, and eventually alleviated proteinuria, inflammation and excessive extracellular matrix deposition in mouse IgAN models. This siRNA co-delivery system thus represents a promising treatment option for IgAN and offers a versatile platform for other glomerular problems. Our work also highlights a novel strategy of glomerulus-targeting and an encouraging therapeutic route for other inflammatory diseases.

Active targeting co-delivery of therapeutic Sur siRNA and an antineoplastic drug via epidermal growth factor receptor-mediated magnetic nanoparticles for synergistic programmed cell death in glioblastoma stem cells

An EGFR-targeted theranostic composite, and targeted co-delivery of therapeutic siRNAs and DOX for glioblastoma stem cell treatments.

Co-delivery of paclitaxel and anti-VEGF siRNA by tripeptide lipid nanoparticle to enhance the anti-tumor activity for lung cancer therapy

The combination of chemotherapeutic drug paclitaxel (PTX) and VEGF siRNA could inhibit cancer development with synergistic efficacy. However, efficient and safe delivery systems with high encapsulation efficiency of PTX and a long-time release of drugs are urgently needed. In this study, novel nanoparticles (PTX/siRNA/FALS) were constructed by using tripeptide lipid (L), sucrose laurate (S), and folate-PEG2000-DSPE (FA) to co-deliver PTX and siRNA. The cancer cell targeting nanoparticle carrier (PTX/siRNA/FALS) showed anticipated PTX encapsulation efficiency, siRNA retardation ability, improved cell uptake and sustained and controlled drug release. It led to significant anti-tumor activity in vitro and in vivo by efficient inhibition of VEGF expression and induction of cancer cell apoptosis. Importantly, the biocompatibility of the carriers and low dosage of PTX required for effective therapy greatly reduced the toxicity to mice. The targeting nanoparticles show potential as an effective co-delivery platform for RNAi and chemotherapy drugs, aiming to improve the efficacy of cancer therapy.