Cell Targeting Capability Research Articles

Synthesis of Lactosyl Conjugated 6A,6D-Bifunctionalized β -Cyclodextrin Derivatives as Potential Liver Cancer Drug Carriers

Abstract: Transformations of the difunctionalizated cyclodextrin derivatives is a daunting task due to the challenging purification and unambiguous characterization of the final compounds. Lactose has the ability to recognize the liver cells, and the folate receptor (alpha subunit) is overexpressed in multiple tumors, including liver cancer. Therefore, cyclodextrin conjugated with lactose and folic acid should have the liver cell targeting capability, and its inclusion complex with liver cancer drug such as Sorafenib, not only can increase drug ‘s water solubility but also increase the drug’s targeting ability. Fondaparinux as a synthetic heparin may improve the survival of cancer patients, so lactose and Fondaparinux conjugated cyclodextrin derivative can increase drug’s solubility and drug’s anti-tumor efficacy. Accordingly, Fondaparinux, folic acid and lactose conjugated 6A,6D-bifunctionlized β-cyclodextrin derivatives are designed and synthesized as potential liver cancer drug carriers in order to increase cancer drug’s targeting ability, solubility and stability.

Super-resolution imaging of antibody-conjugated biodegradable periodic mesoporous organosilica nanoparticles for targeted chemotherapy of prostate cancer.

Biodegradable periodic mesoporous organosilica nanoparticles (nanoPMOs) are widely used as responsive drug delivery platforms for targeted chemotherapy of cancer. However, the evaluation of their properties such as surface functionality and biodegradability is still challenging, which has a significant impact on the efficiency of chemotherapy. In this study, we have applied direct stochastic optical reconstruction microscopy (dSTORM), a single-molecule super-resolution microscopy technique, to quantify the degradation of nanoPMOs triggered by glutathione and the multivalency of antibody-conjugated nanoPMOs. Subsequently, the effect of these properties on cancer cell targeting, drug loading and release capability, and anticancer activity is also studied. Due to the higher spatial resolution at the nanoscale, dSTORM imaging is able to reveal the structural properties (i.e., size and shape) of fluorescent and biodegradable nanoPMOs. The quantification of nanoPMOs' biodegradation using dSTORM imaging demonstrates their excellent structure-dependent degradation behavior at a higher glutathione concentration. The surface functionality of anti-M6PR antibody-conjugated nanoPMOs as quantified by dSTORM imaging plays a key role in prostate cancer cell labeling: oriented antibody is more effective than random ones, while high multivalency is also effective. The higher biodegradability and cancer cell-targeting properties of nanorods conjugated with oriented antibody (EAB4H) effectively deliver the anticancer drug doxorubicin to cancer cells, exhibiting potent anticancer effects.

Sequential Delivery of Novel Triple Drug Combination via Crosslinked Alginate/Lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment.

While breast cancer remains a global health concern, the elaboration of rationally designed drug combinations coupled with advanced biocompatible delivery systems offers new promising treatment venues. Herein, we repurposed rosuvastatin (RST) based on its selective tumor apoptotic effect and combined it with the antimetabolite pemetrexed (PMT) and the tumor-sensitizing polyphenol honokiol (HK). This synergistic three-drug combination was incorporated into protein polysaccharide nanohybrids fabricated by utilizing sodium alginate (ALG) and lactoferrin (LF), inspired by the stealth property of the former and the cancer cell targeting capability of the latter. ALG was conjugated to PMT and then coupled with LF which was conjugated to RST, forming core shell nanohybrids into which HK was physically loaded, followed by cross linking using genipin. The crosslinked HK-loaded PMT-ALG/LF-RST nanohybrids exhibited a fair drug loading of 7.86, 5.24 and 6.11% for RST, PMT and HK, respectively. It demonstrated an eight-fold decrease in the IC50 compared to the free drug combination, in addition to showing an enhanced cellular uptake by MCF-7 cells. The in vivo antitumor efficacy in a breast cancer-bearing mouse model confirmed the superiority of the triple cocktail-loaded nanohybrids. Conclusively, our rationally designed triple drug-loaded protein/polysaccharide nanohybrids offer a promising, biocompatible approach for an effective breast tumor suppression.

Drug-Loaded Acoustic Nanodroplet for Dual-Imaging Guided Highly Efficient Chemotherapy Against Nasopharyngeal Carcinoma.

BackgroundChemotherapy is an important approach to treating nasopharyngeal carcinoma (NPC). Unfortunately, the lack of selectivity, insufficient tumor accumulation, uneven tumor distribution and severe systemic toxicity lead to the unsatisfactory performance of these drugs. While a more precise drug delivery, on-demand drug release, and deep diffusion of drugs (homogeneous distribution of drugs in the tumor) could improve the application, they remain challenging. Chemotherapeutic drug-loaded acoustic nanodroplet with dual-imaging capacity is expected to solve these problems.MethodsFolate (Fa)-modified and doxorubicin (Dox)-loaded acoustic poly (lactic‐co‐glycolic acid) (PLGA), low intensity focused ultrasound (LIFU)-responsive perfluoropentane (PFP) and Fe3O4 nanoparticles (designated as Fa-Fe@P-PFP-Dox) were integrated by a double-emulsion method. After the synthesis, the LIFU-triggered acoustic droplet vaporization (ADV) effect, LIFU-triggered drug release, cell targeting capability, in vitro cell-killing effects, biodistribution, PA/MR dual imaging (PA: photoacoustic; MR: magnetic resonance), LIFU-augmented Dox distribution in tumors and chemotherapeutic efficacy of Fa-Fe@P-PFP-Dox were investigated.ResultsThe distribution of these drug-loaded nanodroplets was clearly monitored via PA/MR dual imaging. Upon LIFU irradiation, PFP within the Fa-Fe@P-PFP-Dox nanodroplets underwent ADV, which led to the release of Dox and promoted the deep penetration of Dox in tumor tissue, eventually achieving highly efficient chemotherapy against NPC. As a result, LIFU-triggered chemotherapy exerted a highly efficient therapeutic effect with a tumor inhibition rate of 74.24 ± 7.95%.ConclusionFa-modified and drug-loaded acoustic nanodroplets have been successfully constructed for dual-imaging guided highly efficient chemotherapy against NPC. This novel tumor drug delivery method is expected to provide an efficient, visualized, and precise personalized treatment method for NPC patients with minimal side effects.

Structural control of self-assembled peptide nanostructures to develop peptide vesicles for photodynamic therapy of cancer.

Vesicles such as liposomes, polymersomes, and exosomes have been widely used as drug delivery carriers; however, peptide vesicles (peptidesomes) despite their potential utility are far less well developed. Peptidesomes are distinctive because peptides play dual roles as a self-assembly building block and a bioactive functional unit. In order for peptidesomes to become successful nanodrugs, the issues related to differences in nanostructural properties between in vitro and in vivo conditions should be addressed. Here, we delineate a multivariate approach to feedback control the structures of peptide building blocks, nanoparticle size, drug loading process, nanoparticle aggregation, cytotoxicity, cell targeting capability, endosome disruption function, protease resistance, and in vivo performance, which eventually enabled the successful development of a highly efficacious peptidesome for in vivo cancer therapy. This study lays the groundwork for the successful in vivo translation of peptide nanodrugs.

Quantification of Available Ligand Density on the Surface of Targeted Liposomal Nanomedicines at the Single-Particle Level.

Active targeting has been hailed as one of the most promising strategies to further enhance the therapeutic efficacy of liposomal nanomedicines. Owing to the critical role of ligand density in mediating cellular uptake and the intrinsic heterogeneity of liposomal formulations, precise quantification of the surface ligand density on a single-particle basis is of fundamental importance. In this work, we report a method to simultaneously measure the particle size and the number of ligands on the same liposomal nanoparticles by nanoflow cytometry. Then the ligand density for each individual liposome can be determined. With an analysis rate up to 10 000 particles per minute, a statistically representative distribution of ligand density could be determined in minutes. By utilizing fluorescently labeled recombinant receptors as the detection probe against the conjugated ligands, only those available for cell targeting can be exclusively detected. The influence of ligand input, conjugation strategy, and the polyethylene glycol spacer length on the available ligand density of folate-modified liposomes was investigated. The correlation between the available ligand density and cell targeting capability was assessed in a quantitative perspective for liposomes modified with three different targeting moieties. The optimal ligand density was determined to be 0.5-2.0, 0.7, and 0.2 ligand per 100 nm2 for folate-, transferrin-, and HER2-antibody-conjugated liposomes, respectively. These optimal values agreed well with the spike density of the natural counterparts, viruses. The as-developed approach is generally applicable to a wide range of active-targeting nanocarriers.

Small Molecular Prodrug Amphiphile Self-Assembled AIE Dots for Cancer Theranostics.

A simple and facile one-step method was developed to construct a small molecular prodrug amphiphile self-assembled organic dots CPPG with aggregation-induced emission (AIE) characteristics. Diphenylalanine peptide (FF), which is the essential moiety of the self-assembling peptide-drug conjugate and as its core recognition motifs for molecular self-assembly. In addition, the D-glucose transported protein (GLUT), which is one of the important nutrient transporters and is overexpressed in cancer cells. The conjugation of glycosyl further endues the nanoparticle with good biocompatibility and tumor-targeting ability. Taking advantages of both the cancer cell-targeting capability of small molecular prodrug amphiphile CPPG and the AIE aggregates with strong emission, the prepared CPPG AIE dots can target cancer cells specifically and inhibit the proliferation of cancer cells with good biocompatibility and photostability. Based on the general approach, types of universal organic fluorescent nanoprobes could be facilely constructed for imaging applications and biological therapeutics, which possess the properties of specific recognition and high brightness.

Rigidified DNA Triangle-Protected Molecular Beacon from Endogenous Nuclease Digestion for Monitoring microRNA Expression in Living Cells

Utilizing the nucleic acid-based self-assembly technology, Y-shaped backbone-rigidified DNA triangles with substantially enhanced nuclease resistance are built by designing a Y-shaped backbone in the center of a planar DNA triangle. Along this line, we developed aptamer-targeted DNA triangle-based molecular beacon (Apt-Tri-MB) probes for monitoring the microRNA expression in living cells with high sensitivity and specificity. For the Apt-Tri-MB probe, the MB is protected by the DNA triangle from unwanted enzymatic digestion, and a targeting ligand aptamer is introduced to endow the MB with active tumor cell-targeting capability. Thus, the digestion-induced false-positive signal is avoided, and the background fluorescence, which originates from the passive cell uptake (e.g., transfection) of reporting probes, is substantially suppressed. The imaging capability of the Apt-Tri-MB is superior to the commercial transfection agent-based counterpart and exhibits good universality suitable for imaging different miRNAs by changing the recognition fragment of the MB. Meanwhile, the disadvantages are efficiently circumvented, including the susceptibility of nucleic acids to nuclease-mediated degradation, inability of MB probes to enter cells, lipofectamine-determined cellular cytotoxicity, and nontargeting cell uptake. Inspired by the Y-shaped backbone-rigidified Apt-Tri-MB, we also constructed X-shaped backbone-rigidified quadrangle-based probes (Apt-Qua-MB). The experimental results show that cell imaging and antidegradation capability of Apt-Qua-MB are comparable with Apt-Tri-MB. As a proof-of-concept study, the Apt-Tri-MB is expected to open an exciting avenue for the further application of nucleic acid probes in the cellular level research and clinical disease diagnosis.

Cancer Cell-Targeted Photosensitizer and Therapeutic Protein Co-Delivery Nanoplatform Based on a Metal-Organic Framework for Enhanced Synergistic Photodynamic and Protein Therapy.

Efficient and cancer cell-targeted delivery of photosensitizer (PS) and therapeutic protein has great potentiality for improving the anticancer effects. Herein, zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, one of the most attractive metal-organic framework materials, were used for coencapsulating the chlorin e6 (Ce6, a potent PS) and cytochrome c (Cyt c, a protein apoptosis inducer); then the nanoparticle was subsequently decorated with the hyaluronic acid (HA) shell to form cancer cell-active targeted nanoplatform (Ce6/Cyt c@ZIF-8/HA). The in vitro and in vivo experiments show the cancer cell targeting capability and pH-responsive decomposition and the release behavior of Ce6/Cyt c@ZIF-8/HA. Upon light irradiation, the released Ce6 produced cytotoxic reactive oxygen species for photodynamic therapy. Meanwhile, the released Cyt c-induced programmed cell death for protein therapy. Furthermore, the Cyt c worked normally under hypoxia conditions and could decompose H2O2 to O2 (with peroxidase-/catalase-like activity), resulting in synergistically improved therapeutic efficiency. These small molecules and protein codelivery nanoplatforms would promote the development of complementary and synergetic modes for biomedical applications.

Sequentially-targeted biomimetic nano drug system for triple-negative breast cancer ablation and lung metastasis inhibition

As a breast cancer subtype with high mortality in women, the efficient treatment of Triple-negative breast cancer (TNBC) is still a challenge due to its unique metastatic mode and poor prognosis. In this study, we developed a biomimetic nanodelivery system (denoted as GTDC@M-R NPs) based on erythrocyte membrane (M)-camouflaged graphene oxide quantum dots (GOQDs, G) for TNBC therapy. The TAT (T) and RGD (R) peptides were used to endow targeting accumulation ability of Gamabufotalin (CS-6, C) and doxorubicin (DOX, D) in tumor tissue. In vitro assay indicated good biocompatibility, prolonged blood circulation time (3-fold longer than GT NPs), and effectively enhanced cell and nucleus targeting capability of this nanosystem. Fluorescence activated cell sorter (FACS) analysis indicated that the combination of DOX and CS-6 induced TNBC cell apoptosis more than 89 % under the ratio of 10:1. In vivo assay indicated that the accumulation of GTDC@M-R NPs in tumor sites increased about 2-fold compared to naked GTDC NPs, which was accompanied by high tumor apoptosis rates through blocking chemotherapy-activated cyclooxygenase-2 (COX-2) and enhancing DOX's anti-tumor activity of chemical drugs (85%). Moreover, comparing with the control, the average number of lung metastatic nodules in tumor-bearing mice reduced 84%, the molecular mechanism of which is related to the down expression of COX-2, matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF). Taken together, our results proved that the developed GTDC@M-R NPs can inhibit the growth and suppress metastasis of TNBC, which broaden our insights into the application of combinational strategy for efficient TNBC therapy. Statement of SignificanceIn this study, we developed a biomimetic nanodelivery system (denoted as GTDC@M-R NPs) based on erythrocyte membrane (M)-camouflaged graphene oxide quantum dots (GOQDs, G) for TNBC therapy. The TAT (T) and RGD (R) peptides were used to endow targeting accumulation ability of Gamabufotalin (CS-6, C) and doxorubicin (DOX, D) in tumor tissue. These GTDC@M-R NPs indicated synergistic chemotherapy against TNBC cells through the precise cell and nuclear targeting, immune escape, and improved DOX sensitivity. A effective inhibition of tumor growth and metastasis was achieved by inhibiting Bcl-2/BAX, COX-2 and VEGF related signal pathways. Our finding suggests that the developed GTDC@M-R NPs present great treating effects in the preclinical models of TNBC, which broaden our insights into the application of combinational strategy for efficient TNBC therapy.

Non-signaling Chimeric Antigen Receptors Enhance Antigen-Directed Killing by γδ T Cells in Contrast to αβ T Cells

Chimeric antigen receptor (CAR)-modified T cells have demonstrated efficacy against B cell leukemias/lymphomas. However, redirecting CAR T cells to malignant T cells is more challenging due to product-specific cis- and trans-activation causing fratricide. Other challenges include the potential for product contamination and T cell aplasia. We expressed non-signaling CARs (NSCARs) in γδ T cells since donor-derived γδ T cells can be used to prevent product contamination, and NSCARs lack signaling/activation domains, but retain antigen-specific tumor cell-targeting capability. As a result, NSCAR targeting requires an alternative cytotoxic mechanism, which can be achieved through utilization of γδ T cells that possess major histocompatibility complex (MHC)-independent cytotoxicity. We designed two distinct NSCARs and demonstrated that they do not enhance tumor-killing by αβ T cells, as predicted. However, both CD5-NSCAR- and CD19-NSCAR-modified γδ T cells enhanced cytotoxicity against T and B cell acute lymphoblastic leukemia (T-ALL and B-ALL) cell lines, respectively. CD5-NSCAR expression in γδ T cells resulted in a 60% increase in cytotoxicity of CD5-expressing T-ALL cell lines. CD19-NSCAR-modified γδ T cells exhibited a 350% increase in cytotoxicity against a CD19-expressing B-ALL cell line compared to the cytotoxicity of naive cells. NSCARs may provide a mechanism to enhance antigen-directed anti-tumor cytotoxicity of γδ T cells through the introduction of a high-affinity interaction while avoiding self-activation.

Enzymatic synthesis of PEGylated lactide-diester-diol copolyesters for highly efficient targeted anticancer drug delivery

PEGylated lactide-diester-diol copolymers were successfully synthesized via lipase-catalyzed copolymerization, the resultant amphiphilic PEG-poly(L-lactate-co-hexamethylene-co-adipate) (PEG-PLLHA) and PEG-poly(D,L-lactate-co-hexamethylene-co-adipate) (PEG-PDLLHA) block copolymers readily undergo self-assembly processes to form nanosized micelles in aqueous medium, which are stable under physiological conditions in the presence of serum proteins. By conjugating folic acid (FA) to enzymatic synthesized poly(hexamethylene adipate-co-hexamethylene 2,3-epoxy succinate), we could formulate FA-bearing PEG-polyester micelles for docetaxel (DTX) targeting delivery. FA-PEG-PLLHA and FA-PEG-PDLLHA micelles possess efficient cell-targeting capability toward FA receptor-positive cancer cells (e.g., CT-26), which significantly enhances their cellular uptake rates and efficacy of drug-loaded formulations toward such cells. During in vivo anticancer treatments, the FA-bearing micelles are highly capable of targeting and accumulating preferentially in tumor tissues by both active cell-targeting mechanism and passive targeting via the EPR effect. All these desirable properties enable the FA-bearing micelles to deliver DTX with 97% tumor-inhibiting efficiency through systemic delivery, which is favorable in comparison to the values of various DTX nanoparticle formulations reported in literature. Importantly, biosafety assays reveal that all DTX-loaded micelles are biocompatible and safe for in vivo antitumor treatment applications. Thus, FA-PEG-PLLHA and FA-PEG-PDLLHA micelles represent new types of promising anticancer drug nanocarriers for targeted chemotherapy.

Herceptin-decorated paclitaxel-loaded poly(lactide-co-glycolide) nanobubbles: ultrasound-facilitated release and targeted accumulation in breast cancers

Ultrasound can promote the drug release from drug-loaded substances and alter the tumor local microenvironment to facilitate the transport of drug carriers into the tumor tissues. Based on the altered tumor microenvironment, nanobubbles (NBs) as drug carriers with surfaces functionalized with targeting ligands can reach the tumor sites, thereby increasing the efficacy of chemotherapy. Herein, paclitaxel (PTX)-loaded poly(lactide-co-glycolide) (PLGA) NBs are prepared as drug carriers with covalently conjugated herceptin (anti-HER2 monoclonal antibody) on the surface to guide the target. The effect of ultrasound on the drug release and targeting of the herceptin-conjugated drug-loaded nanobubbles (PTX-NBs-HER) on the cancerous cells is determined. The use of ultrasound significantly improves the cell targeting capability in vitro, and efficiency of enhanced permeability and retention in vivo. The combination of PTX-NBs-HER and ultrasound facilitates the release of PTX, as well as the uptake and cell apoptosis in vitro. The in vivo application of both PTX-NBs-HER and ultrasound enhances the PTX targeting and accumulation in breast cancers while reducing the transmission and distribution of PTX in healthy organs. The combination of ultrasound with PTX-NBs-HER as contrast agents and drug carriers affords an image-guided drug delivery system for the precise targeted therapy of tumors.

Host-guest fabrication of dual-responsive hyaluronic acid/mesoporous silica nanoparticle based drug delivery system for targeted cancer therapy

In this paper, a targeting hyaluronic acid (HA)/mesoporous silica nanoparticle (MSN) based drug delivery system (DDS) with dual-responsiveness was prepared for cancer therapy. To avoid the side reaction between the anti-cancer drug doxorubicin hydrochloride (DOX) and HA, host-guest interaction was applied to fabricate the DDS named DOX@MSN-SS-N=C-HA. The “nanocontainer” MSN was modified with benzene ring via both pH-sensitive benzoic imine bond and redox-sensitive disulfide linkage. When DOX was loaded in the pores of MSN, the channels were then capped by the “gatekeeper” β-CD grafted HA (HA-g-CD) through host-guest interaction between β-CD and benzene. HA endowed the drug carriers with the targeting capability in CD44 over-expressed cancer cells. After cellular uptake, the carriers could rapidly release DOX for cell apoptosis due to both the hydrolysis of benzoic imine bond at low pH and the cleavage of disulfide bond at a high concentration of glutathione (GSH) intracellular. In vitro drug release studies and in vitro cytotoxicity studies were taken to investigate the dual-responsiveness of the carriers. And the CD44-receptor mediated cancer cell targeting capability was investigated as well. In conclusion, the targeted dual-responsive complex DDS fabricated through host-guest interaction has promising potential in cancer therapy.

Aptamer-Anchored Rubrene-Loaded Organic Nanoprobes for Cancer Cell Targeting and Imaging

Aptamer-Anchored Rubrene-Loaded Organic Nanoprobes for Cancer Cell Targeting and Imaging

MiRNA-181a over-expression in mesenchymal stem cell-derived exosomes influenced inflammatory response after myocardial ischemia-reperfusion injury

AimsThe inflammation modulation effects of mesenchymal stromal cell-derived exosomes (MSC-EXO) are well established. We aimed to explore the mechanism behind the inflammatory responses of numerous exosomal cargo molecules that have been neglected in molecular biology research, and to develop an exosomal cargo delivery system that can exert a stronger therapeutic effect on myocardial ischemia-reperfusion (I/R) injury. Main methodsComputational approaches were used to identify key exosomal miRNAs and their downstream mRNAs that are expressed in the inflammatory response. Direct interactions between miRNA-181a and the c-Fos mRNA complex were confirmed by luciferase reporter assay. MSC-EXO carrying miRNA-181a-overexpressing lentiviruses were intramyocardially injected into a mouse model of myocardial I/R injury. I/R progression was evaluated through echocardiography and immunofluorescence microscopy. Key findingsmiRNA-181a provided substantial coverage against a host of immune-related genes through the miRNA-mRNA network. miRNA-181a delivery by MSC-EXO combined the immune-suppressing effect of miRNA-181a and the cell targeting capability of MSC-EXO to exert a stronger therapeutic effect on myocardium I/R injury. SignificanceWe showed the potential of MSC-EXO as a tool for the specific delivery of small RNAs in vivo. This study shed new light on the potential application of miRNA-181a-overexpressing MSC-EXO as a therapeutic strategy for myocardial I/R injury.

A Dual-Targeting Delivery System for Effective Genome Editing and In Situ Detecting Related Protein Expression in Edited Cells.

One of critical steps in genome editing by CRISPR-Cas9 is to deliver the CRISPR-Cas9 system into targeted cells. In this study, we developed a dual-targeting delivery system based on polymer/inorganic hybrid nanoparticles to realize highly efficient genome editing in targeted tumor cells as well as in situ detection on the related protein expression in edited cells. The CRISPR-Cas9 plasmid for CDK11 knockout was encapsulated in the core of the delivery system composed of protamine sulfate, calcium carbonate, and calcium phosphate by coprecipitation, and functional derivatives of carboxymethyl chitosan (biotinylated carboxymethyl chitosan with biotin ligands and aptamer-incorporated carboxymethyl chitosan with AS1411 ligands) were decorated on the nanovector surface by electrostatic interactions to form the dual-targeting delivery system. On the basis of the tumor cell targeting capability of biotin and AS1411 ligands as well as the nuclear targeting of AS1411, the dual-targeting system can deliver the CRISPR-Cas9 plasmid into the nuclei of tumor cells to realize highly efficient genome editing, resulting in a dramatic decrease (>90%) in CDK11 protein together with the significant downregulation of other proteins involved in tumor development, including an ∼90% decrease in MMP-9, >40% decrease in VEGF, and ∼70% decrease in survivin. Using the same vector, molecular beacons can be easily delivered to edited cell nuclei to in situ detect the mRNA level of related proteins (p53 and survivin as typical examples) and mRNA distribution in subcellular organelles. Our strategy can realize effective genome editing and in situ detection on related protein expression simultaneously.

An oxaliplatin(iv) prodrug-based supramolecular self-delivery nanocarrier for targeted colorectal cancer treatment.

A redox-responsive supramolecular nanocarrier was constructed from the self-assembly of spermine modified cyclodextrin and oxaliplatin prodrug. The nanocarrier could preferentially accumulate in polyamine transporter over-expressing HCT116 cells, releasing drugs under a reducing intracellular environment to maximize anticancer treatment.

Aptamer-Decorated Self-Assembled Aggregation-Induced Emission Organic Dots for Cancer Cell Targeting and Imaging.

A facile and simple one-step method was developed to fabricate aptamer-decorated self-assembled organic dots with aggregation-induced emission (AIE) characteristics. With integration of the advantages of AIE aggregates with strong emission and the cell-targeting capability of aptamers, the as-prepared Apt-AIE organic nanodots can specifically target to cancer cells with good biocompatibility, high image constrast, and photostability. On the basis of this universal method, a variety of versatile organic fluorescent nanoprobes with high brightness, specific recognition, and clinical-transitional potential could be facilely constructed for biological sensing and imaging applications.

Biodegradable, multifunctional DNAzyme nanoflowers for enhanced cancer therapy

Safety and efficiency remain the critical hurdles hindering the practical application of gene agents, even though great effort has been made to develop various gene carriers. Herein, we present a novel biodegradable cancer therapeutic system based on DNA nanoflowers (DNFs) for targeted dual gene silencing. The therapeutic system was constructed by copying a rolling circle amplification template to produce long single-stranded DNAs with cell targeting and dual gene-silencing capability. The structure of the DNFs collapsed at acidic pH due to the decomposition of the co-assembled magnesium pyrophosphate, generating Mg2+ ions that act as cofactors for the DNAzymes and increase their ability to recognize and cleave target mRNAs. In vitro and in vivo studies demonstrated that the multifunctional DNFs showed promise for targeted cancer cell recognition, gene silencing, induction of apoptosis and inhibition of tumor growth. Considering the enhanced therapeutic effect and biocompatibility of this therapeutic platform, it is anticipated to be of great interest for the clinical treatment of cancers.