Tumor-targeted Drug Delivery Systems Research Articles

Synthesis and Biopharmaceutical Evaluation of Nanoparticles Containing Resveratrol, an Anti-cancer Drug

The chemotherapy of cancer disease become increasingly important in recent years because ease of operation. The traditional cancer chemotherapy is based on the promise that tumor cells are more likely to be killed by anticancer drugs because of the faster proliferation of those cancer cells. However, in reality most of the drugs cannot differentiate cancer cells from the normal cells. This result the undesirable effect of the drug because of the lack of selectivity i.e the patients always at risk of cytotoxicity. So the development of tumor targeted drug delivery systems in which they recognize the intrinsic difference between normal cells and tumor cells is an important requirement for effective tumor therapy. These carriers include nanoparticles, nanotubes, Nano rods, centromeres, micelles, solid lipid nanoparticles, microspheres. In this experiment, all the materials used in the experiments were of analytical grade. Synthesis of CDI-activated poloxamer-407, NH2 terminated poloxamer-407,Folate conjugated poloxamer-407 and prototype formulation of Liquid crystalline nanoparticle were prepared. Drug loading was done with the optimized formula. In vitro drug release from the nanoparticles was determined in phosphate buffer pH 7.4 and Zero-order model, first order model, Higuchi’s model, kosmeyer-Peppas model also tried for compatibility. The cytotoxicity studies in the final formula by Brine shrimp experiments were done and found that it is significant. There are only 0.01% differences in each case. It was found that in-vitro drug release of resveratrol from optimized LCN at pH 7.4 and pH5 was best explained by Higuchi’s equation, as the plot showed the highest linearity with a regression coefficient of 0.9528 and 0.9404 respectively. The entrapment efficiency of optimized LCN was found to be 87.43 ± 0.52 % which was in close agreement with the value predicted by design expert software. It was found that the invitro drug release of resveratrol from optimized LCN at pH 7.4 and pH 5 was best explained by Higuchi’s equation, as the plot showed the highest linearity with a regression coefficient of 0.9528 and 0.9404 respectively.

Sustained and Targeted Delivery of Self-Assembled Doxorubicin Nonapeptides Using pH-Responsive Hydrogels for Osteosarcoma Chemotherapy

While chemotherapeutic agents have particularly potent effects in many types of cancer, their clinical applications are still far from satisfactory due to off-target drug exposure, chemotherapy resistance, and adverse effects, especially in osteosarcoma. Therefore, it is clinically promising to construct a novel tumor-targeted drug delivery system to control drug release and alleviate side effects. In this study, a pH-responsive nonapeptide hydrogel was designed and fabricated for the tumor-targeted drug delivery of doxorubicin (DOX). Using a solid-phase synthesis method, a nonapeptide named P1 peptide that is structurally akin to surfactant-like peptides (SLPs) due to its hydrophobic tail and hydrophilic head was synthesized. The physicochemical properties of the P1 hydrogel were characterized via encapsulation capacity, transmission electron microscopy (TEM), circular dichroism (CD), zeta potential, rheological analysis, and drug release studies. We also used in vitro and in vivo experiments to investigate the cytocompatibility and tumor inhibitory efficacy of the drug-loaded peptide hydrogel. The P1 peptide could self-assemble into biodegradable hydrogels under neutral conditions, and the prepared drug-loaded hydrogels exhibited good injectability and biocompatibility. The in vitro drug release studies showed that DOX-P1 hydrogels had high sensitivity to acidic conditions (pH 5.8 versus 7.4, up to 3.6-fold). Furthermore, the in vivo experiments demonstrated that the DOX-P1 hydrogel could not only amplify the therapeutic effect but also increase DOX accumulation at the tumor site. Our study proposes a promising approach to designing a pH-responsive hydrogel with controlled doxorubicin-release action based on self-assembled nonapeptides for targeted chemotherapy.

Multifunctional Graphene Oxide Nanodelivery Platform for Breast Cancer Treatment.

Breastcancer(BC) has the highest global prevalence among all malignancies in women and the second highest prevalence in the overall population. Paclitaxel(PTX),atricyclicditerpenoid, is effective against BC. However, its poor solubility in water and the allergenicity of its dissolution medium limited itsclinicalapplication. In this work, we established a multifunctional graphene oxide (GO) tumor-targeting drug delivery system using nanosized grapheneoxide(nGO) modified with D-tocopherol polyethylene glycol succinate (TPGS) and arginine-glycine-asparticacid(RGD) for PTX loading. The obtained RGD-TPGS-nGO-PTX was 310.20±19.86 nm in size; the polydispersity index (PDI) and zeta potential were 0.21±0.020 and -23.42 mV, respectively. Themeandrugloading capacityof RGD-TPGS-nGO-PTX was 48.78%. RGD-TPGS-nGO-PTX showed satisfactory biocompatibility and biosafety and had no significant toxic effects on zebrafish embryos. Importantly, it exerted excellent cytotoxicity against MDA-MB-231 cells, reversed multi-drug resistance (MDR) in MCF-7/ADR cells, and showed significant anti-tumor efficacy in tumor-bearing nude mice. These findings strongly suggested that the multifunctional GO tumor-targeting drug delivery system RGD-TPGS-nGO-PTX could be used in clinical settings to improve PTX delivery, reverse MDR and increase the therapeutic efficacy of BC treatment.

A Novel Dextran-Based Dual Drug Conjugate Targeted Tumors with High Biodistribution Ratio of Tumors to Normal Tissues.

PurposeMost chemotherapeutic agents possess poor water solubility and show more significant accumulations in normal tissues than in tumor tissues, resulting in serious side effects. To this end, a novel dextran-based dual drug delivery system with high biodistribution ratio of tumors to normal tissues was developed.MethodsA bi-functionalized dextran was developed, and several negatively charged dextran-based dual conjugates containing two different types of drugs, docetaxel and docosahexaenoic acid (DTX and DHA, respectively) were synthesized. The structures of these conjugates were characterized using nuclear magnetic resonance and liquid chromatography/mass spectrometry (1H-NMR and LC/MS, respectively) analysis. Cell growth inhibition, apoptosis, cell cycle distribution, and cellular uptake were measured in vitro. Drug biodistribution and pharmacokinetics were investigated in mice bearing 4T1 tumors using LC/MS analysis. Drug biodistribution was also explored by in vivo imaging. The effects of these conjugates on tumor growth were evaluated in three mice models.ResultsThe dextran–docosahexaenoic acid (DHA)– docetaxel (DTX) conjugates caused a significant enhancement of DTX water solubility and improvement in pharmacokinetic characteristics. The optimized dextran–DHA–DTX conjugate A treatment produced a 2.1- to 15.5-fold increase in intra-tumoral DTX amounts for up to 96 h compared to parent DTX treatment. Meanwhile, the concentrations of DTX released from conjugate A in normal tissues were much lower than those of the parent DTX. This study demonstrated that DHA could lead to an improvement in the efficacy of the conjugates and that the conjugate with the shortest linker displayed more activity than conjugates with longer linkers. Moreover, conjugate A completely eradicated all MCF-7 xenograft tumors without causing any obvious side effects and totally outperformed both the conventional DTX formulation and Abraxane in mice.ConclusionThese dextran-based dual drug conjugates may represent an innovative tumor targeting drug delivery system that can selectively deliver anticancer agents to tumors.

Hyaluronic Acid-Based Nanomaterials Applied to Cancer: Where Are We Now?

Cancer cells normally develop the ability to rewire or reprogram themselves to become resistant to treatments that were previously effective. Despite progress in understanding drug resistance, knowledge gaps remain regarding the underlying biological causes of drug resistance and the design of cancer treatments to overcome it. So, resistance acquisition remains a major problem in cancer treatment. Targeted therapeutics are considered the next generation of cancer therapy because they overcome many limitations of traditional treatments. Numerous tumor cells overexpress several receptors that have a high binding affinity for hyaluronic acid (HA), while they are poorly expressed in normal body cells. HA and its derivatives have the advantage of being biocompatible and biodegradable and may be conjugated with a variety of drugs and drug carriers for developing various formulations as anticancer therapies such as micelles, nanogels, and inorganic nanoparticles. Due to their stability in blood circulation and predictable delivery patterns, enhanced tumor-selective drug accumulation, and decreased toxicity to normal tissues, tumor-targeting nanomaterial-based drug delivery systems have been shown to represent an efficacious approach for the treatment of cancer. In this review, we aim to provide an overview of some in vitro and in vivo studies related to the potential of HA as a ligand to develop targeted nanovehicles for future biomedical applications in cancer treatment.

Polymeric micelles and cancer therapy: an ingenious multimodal tumor-targeted drug delivery system.

Since the beginning of pharmaceutical research, drug delivery methods have been an integral part of it. Polymeric micelles (PMs) have emerged as multifunctional nanoparticles in the current technological era of nanocarriers, and they have shown promise in a range of scientific fields. They can alter the release profile of integrated pharmacological substances and concentrate them in the target zone due to their improved permeability and retention, making them more suitable for poorly soluble medicines. With their ability to deliver poorly soluble chemotherapeutic drugs, PMs have garnered considerable interest in cancer. As a result of their remarkable biocompatibility, improved permeability, and minimal toxicity to healthy cells, while also their capacity to solubilize a wide range of drugs in their micellar core, PMs are expected to be a successful treatment option for cancer therapy in the future. Their nano-size enables them to accumulate in the tumor microenvironment (TME) via the enhanced permeability and retention (EPR) effect. In this review, our major aim is to focus primarily on the stellar applications of PMs in the field of cancer therapeutics along with its mechanism of action and its latest advancements in drug and gene delivery (DNA/siRNA) for cancer, using various therapeutic strategies such as crossing blood-brain barrier, gene therapy, photothermal therapy (PTT), and immunotherapy. Furthermore, PMs can be employed as "smart drug carriers," allowing them to target specific cancer sites using a variety of stimuli (endogenous and exogenous), which improve the specificity and efficacy of micelle-based targeted drug delivery. All the many types of stimulants, as well as how the complex of PM and various anticancer drugs react to it, and their pharmacodynamics are also reviewed here. In conclusion, commercializing engineered micelle nanoparticles (MNPs) for application in therapy and imaging can be considered as a potential approach to improve the therapeutic index of anticancer drugs. Furthermore, PM has stimulated intense interest in research and clinical practice, and in light of this, we have also highlighted a few PMs that have previously been approved for therapeutic use, while the majority are still being studied in clinical trials for various cancer therapies.

A novel ursodeoxycholic acid–chitosan-folate conjugates for the delivery of calcitriol for cancer therapy

The primary drawback of calcitriol (CAL) as an anticancer drug is its induction of hypercalcemia and hyperphosphatemia. Thus, there is an urgent need for the development of targeted delivery systems for improving the safety and efficacy of CAL. In this study, the modification of chitosan was carried out with ursodeoxycholic acid and covalently interacted with folic acid for developing a novel tumor-targeting drug delivery system. The conjugates were structurally characterized via X-ray diffraction, 1H NMR, and Fourier-transform infrared spectroscopy. Fluorescence spectroscopy and zeta potential measurements were used for analyzing the physical as well as chemical properties of the self-aggregates in an aqueous medium. Transmission electron microscopy was carried out for visualizing the surface morphology of self-aggregates. The drug-loading and encapsulation efficiencies and in vitro drug release of the prepared CAL-loaded micelles were further evaluated. MTT assay revealed that the cytotoxicity of folate-micellar CAL (UDCA–CS–FA/CAL) toward mice hepatocellular carcinoma cells was elevated relative to that of micelles without folate or free CAL. The growth of the tumour was significantly attenuated by UDCA–CS–FA/CAL micelles in a xenograft tumorigenesis model. Quantification of serological indicators in UDCA–CS–FA/CAL-treated and control mice showed that CAL-loaded UDCA–CS–FA could be a solution to the side effects of CAL. In conclusion, the UDCA–CS–FA/CAL micelles can be used as an effective approach for CAL-based targeted and safe chemotherapy.

Targeted delivery of doxorubicin by Thermo/pH-responsive magnetic nanoparticles in a rat model of breast cancer

The novel folate conjugated Thermo/pH-responsive magnetic nanoparticles (folate-poly-MNPs) have been developed as a potential nanocarrier for improving site-specific drug delivery, tumor drug accumulation, and therapeutic effects while reducing the adverse effects of conventional drug delivery systems. To evaluate the anticancer efficacy of developed tumor-targeted drug delivery system, forty rat models of breast cancer received saline as control, DOX, DOX-poly-MNPs, and DOX-folate-poly-MNPs at a dose of 2 mg/kg/48 h. The DOX-folate-poly-MNPs showed a significant increase in protein expression of BAX and C-caspase-3 with concomitant downregulation of Bcl-2 expression and ki67 proliferation index compared to the DOX group. The synergistic antitumor efficacy of passive and active drug targeting led to enhanced drug uptake, increased tumor cell apoptosis, decreased tumor volume, and a prolonged survival rate in animals, suggesting that DOX-folate-poly-MNPs may prove to be a promising nanomedicine for the smart treatment of breast cancer in the future.

Nanocarrier-Based Tumor-Targeting Drug Delivery Systems for Hepatocellular Carcinoma Treatments: Enhanced Therapeutic Efficacy and Reduced Drug Toxicity.

Hepatocellular carcinoma (HCC), due to the lack of efficient diagnostic methods and short of available treatments, becomes the third main cause of cancer deaths. Novel treatments for HCCs are thus in great need. The fast-growing area of drug delivery provides intriguing possibility to design nanocarriers with unique properties. The nanocarriers performanced as drug deliver vehicles enable the design of diverse drug delivery systems, which could serve multiple purposes, including improved bioavailability, controlled or triggered release and targeted delivery, leading to enhanced drug efficacy and lowered drug toxicity. This paper provides an overview on the types of delivery vehicles, functions of drug nanocarriers and types of ligand-based targeting systems and highlights the advances made towards better HCC treatments.

Doxorubicin-Loaded Metal-Organic Framework Nanoparticles as Acid-Activatable Hydroxyl Radical Nanogenerators for Enhanced Chemo/Chemodynamic Synergistic Therapy.

Doxorubicin (DOX) is a widely used first-line antitumor agent; however, acquired drug resistance and side effects have become the main challenges to effective cancer therapy. Herein, DOX is loaded into iron-rich metal–organic framework/tannic acid (TA) nanocomplex to form a tumor-targeting and acid-activatable drug delivery system (MOF/TA-DOX, MTD). Under the acidic tumor microenvironment, MTD simultaneously releases DOX and ferrous ion (Fe2+) accompanied by degradation. Apart from the chemotherapeutic effect, DOX elevates the intracellular H2O2 levels through cascade reactions, which will be beneficial to the Fenton reaction between the Fe2+ and H2O2, to persistently produce hydroxyl radicals (•OH). Thus, MTD efficiently mediates chemodynamic therapy (CDT) and remarkably enhances the sensitivity of chemotherapy. More encouragingly, the cancer cell killing efficiency of MTD is up to ~86% even at the ultralow equivalent concentration of DOX (2.26 µg/mL), while the viability of normal cells remained >88% at the same concentration of MTD. Taken together, MTD is expected to serve as drug-delivery nanoplatforms and •OH nanogenerators for improving chemo/chemodynamic synergistic therapy and reducing the toxic side effects.

Shell-Sheddable Micelles Based on Poly(ethylene glycol)-hydrazone-poly[R,S]-3-hydroxybutyrate Copolymer Loaded with 8-Hydroxyquinoline Glycoconjugates as a Dual Tumor-Targeting Drug Delivery System.

The development of selective delivery of anticancer drugs into tumor tissues to avoid systemic toxicity is a crucial challenge in cancer therapy. In this context, we evaluated the efficacy of a combination of nanocarrier pH-sensitivity and glycoconjugation of encapsulated drugs, since both vectors take advantage of the tumor-specific Warburg effect. Herein, we synthesized biodegradable diblock copolymer, a poly(ethylene glycol)-hydrazone linkage-poly[R,S]-3-hydroxybutyrate, which could further self-assemble into micelles with a diameter of ~55 nm. The hydrazone bond was incorporated between two copolymer blocks under an acidic pH, causing the shell-shedding of micelles which results in the drug’s release. The micelles were stable at pH 7.4, but decompose in acidic pH, as stated by DLS studies. The copolymer was used as a nanocarrier for 8-hydroxyquinoline glucose and galactose conjugates as well as doxorubicin, and exhibited pH-dependent drug release behavior. In vitro cytotoxicity, apoptosis, and life cycle assays studies of blank and drug-loaded micelles were performed on Normal Human Dermal Fibroblasts-Neonatal (NHDF-Neo), colon carcinoma (HCT-116), and breast cancer (MCF-7) for 24, 48, and 72 h. A lack of toxicity of blank micelles was demonstrated, whereas the glycoconjugates-loaded micelles revealed enhanced selectivity to inhibit the proliferation of cancer cells. The strategy of combining pH-responsive nanocarriers with glycoconjugation of the drug molecule provides an alternative to the modus operandi of designing multi-stimuli nanocarriers to increase the selectivity of anticancer therapy.

Relieving immunosuppression by Endo@PLT targeting anti-angiogenesis to improve the efficacy of immunotherapies.

Low levels of immune infiltrates in the tumor milieu hinder the effectiveness of immunotherapy against immune-cold tumors. In the current work, a tumor-targeting drug delivery system composed of Endo-loaded platelets (Endo@PLT) was developed to relieve immunosuppression by achieving tumor vascular normalization. Endo@PLT reprogrammed the immunostimulatory phenotype, achieving excellent PD-1 immunotherapy in vivo.

Redox sensitive nano-capsules self-assembled from hyaluronic acid-hydroxychloroquine conjugates for CD44-targeted delivery of hydroxychloroquine to combat breast cancer metastasis in vitro and in vivo

Identifying an efficient tumor-targeted drug delivery system is an urgent task for the treatment of metastatic breast cancer. Herein, we report for the first time that a pH and redox dual-responsive polymer prodrug displays prominent inhibition of breast cancer metastasis to the lung. The polymer molecule was synthesized from hyaluronic acid (HA) and hydroxychloroquine (HCQ) through disulfide bonds as redox-sensitive linkers that self-assemble into nanocapsules (HA-ss-HCQ nanocapsules) at pH 7.4. Due to the pKa value of HCQ and built-in disulfide bonds, the nanocapsules were endowed with pH and redox dual-responsive properties. The in vitro drug release curve revealed that HA-ss-HCQ nanocapsules release drugs more quickly under low pH and high redox conditions. Moreover, the nanocapsules displayed active targeting and selectivity to metastatic breast cancer cells. Cellular uptake of Nile red-loaded nanocapsules observed by fluorescence microscopy showed that the nanocapsules exerted significantly enhanced cellular internalization capacity, which was greatly diminished by free HA. The IC50 of HA-ss-HCQ nanocapsules in 4T1 cells was 2.23-fold lower than that of free HCQ. Importantly, wound healing assays and Transwell experiments demonstrated that HA-ss-HCQ nanocapsules greatly inhibited the migration and invasion of 4T1 cells. In particular, the metastasis of 4T1 cells to the lung was also remarkably suppressed by HA-ss-HCQ nanocapsules with minimal toxicity in an in vitro lung metastasis model, which was verified by the detection of macroscopic metastatic nodules and histological examination. In summary, this study provides a promising strategy for active-targeting therapy in metastatic breast cancer.

Combating liver cancer through GO-targeted biomaterials

Hydroxycamptothecin (HCPT) is a topoisomerase I inhibitor, and it has been widely used clinically in the treatment of primary liver cancer, gastric cancer, and other tumors. The clinical application of HCPT is limited by its water solubility, and it has certain toxicity to patients with tumor. Therefore, the effective tumor site accumulation of HCPT is necessary. This work studied the inhibitory effect of HCPT on the proliferation and migration of human liver cancer cells (HepG-2) and used carboxymethyl chitosan (CMC) and hyaluronic acid (HA) to modify graphene oxide (GO) as nano-carrier materials, which load HCPT to achieve a drug delivery system for liver tumors with good biocompatibility and high drug loading. HCPT can significantly inhibit proliferation and migration of HepG-2, enhance the release of reactive oxygen species, reduce mitochondrial membrane potential, and induce apoptosis. The GO-CMC-HA/HCPT drug delivery system enabled HepG-2 to uptake more HCPT, thereby inhibiting its proliferation and improving the efficacy of HCPT in vivo and in vitro. This study explored a potential therapy strategy by preparing a GO-based tumor-targeted drug delivery system.

Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors.

Simple SummaryHydroxypropyl acrylamide polymer-conjugated pirarubicin (P-THP), an innovative polymer-conjugated anticancer agent, theoretically has highly tumor-specific distribution via the enhanced permeability and retention (EPR) effect. While anthracyclines are extremely important in the treatment of most pediatric solid tumors, P-THP may serve as a less toxic and more effective substitute for conventional anthracyclines in both newly diagnosed and refractory/recurrent pediatric cancers.Most pediatric cancers are highly chemo-sensitive, and cytotoxic chemotherapy has always been the mainstay of treatment. Anthracyclines are highly effective against most types of childhood cancer, such as neuroblastoma, hepatoblastoma, nephroblastoma, rhabdomyosarcoma, Ewing sarcoma, and so forth. However, acute and chronic cardiotoxicity, one of the major disadvantages of anthracycline use, limits their utility and effectiveness. Hydroxypropyl acrylamide polymer-conjugated pirarubicin (P-THP), which targets tumor tissue highly selectively via the enhanced permeability and retention (EPR) effect, and secondarily releases active pirarubicin molecules quickly into the acidic environment surrounding the tumor. Although, the latter rarely occurs in the non-acidic environment surrounding normal tissue. This mechanism has the potential to minimize acute and chronic toxicities, including cardiotoxicity, as well as maximize the efficacy of chemotherapy through synergy with tumor-targeting accumulation of the active molecules and possible dose-escalation. Simply replacing doxorubicin with P-THP in a given regimen can improve outcomes in anthracycline-sensitive pediatric cancers with little risk of adverse effects, such as cardiotoxicity. As cancer is a dynamic disease showing intra-tumoral heterogeneity during its course, continued parallel development of cytotoxic agents and molecular targeting agents is necessary to find potentially more effective treatments.

Effects of the surface charge of polyamidoamine dendrimers on cellular exocytosis and the exocytosis mechanism in multidrug-resistant breast cancer cells

BackgroundPolyamidoamine (PAMAM) dendrimer applications have extended from tumor cells to multidrug-resistant tumor cells. However, their transportation in multidrug-resistant tumor cells remains unclear. Herein, we investigated the exocytosis rule and mechanism of PAMAM dendrimers in multidrug-resistant tumor cells.ResultsUsing a multidrug-resistant human breast cancer cell model (MCF-7/ADR), we performed systematic analyses of the cellular exocytosis dynamics, pathways and mechanisms of three PAMAM dendrimers with different surface charges: positively charged PAMAM-NH2, neutral PAMAM-OH and negatively charged PAMAM-COOH. The experimental data indicated that in MCF-7/ADR cells, the exocytosis rate was the highest for PAMAM-NH2 and the lowest for PAMAM-OH. Three intracellular transportation processes and P-glycoprotein (P-gp) participated in PAMAM-NH2 exocytosis in MCF-7/ADR cells. Two intracellular transportation processes, P-gp and multidrug resistance (MDR)-associated protein participated in PAMAM-COOH exocytosis. P-gp and MDR-associated protein participated in PAMAM-OH exocytosis. Intracellular transportation processes, rather than P-gp and MDR-associated protein, played major roles in PAMAM dendrimer exocytosis. PAMAM-NH2 could enter MCF-7/ADR cells by forming nanoscale membrane holes, but this portion of PAMAM-NH2 was eliminated by P-gp. Compared with PAMAM-OH and PAMAM-COOH, positively charged PAMAM-NH2 was preferentially attracted to the mitochondria and cell nuclei. Major vault protein (MVP) promoted exocytosis of PAMAM-NH2 from the nucleus but had no effect on the exocytosis of PAMAM-OH or PAMAM-COOH.ConclusionsPositive charges on the surface of PAMAM dendrimer promote its exocytosis in MCF-7/ADR cells. Three intracellular transportation processes, attraction to the mitochondria and cell nucleus, as well as nuclear efflux generated by MVP led to the highest exocytosis observed for PAMAM-NH2. Our findings provide theoretical guidance to design a surface-charged tumor-targeting drug delivery system with highly efficient transfection in multidrug-resistant tumor cells. Especially, to provide more DNA to the nucleus and enhance DNA transfection efficiency in multidrug-resistant tumor cells using PAMAM-NH2, siRNA-MVP or an inhibitor should be codelivered to decrease MVP-mediated nuclear efflux.Graphical abstract

Construction and evaluation of red blood cells-based drug delivery system for chemo-photothermal therapy

In this study, a novel tumor-targeting drug delivery system (DDS) based on red blood cells (RBCs) were fabricated for combinational chemo-phototherapy against cancer. Cyclic peptide (cRGD) and indocyanine green (ICG) were applied to the surface of RBCs to increase the targeting and photothermal effect, respectively. Doxorubicin (DOX) as a model drug was loaded into RBCs by the hypotonic dialysis method. A series of tests have been carried out to evaluate the RBCs-based DDS and these tasks include physicochemical properties, cellular uptake, targeting ability, and combination therapeutic efficiency. As a result, the DOX was successfully loaded into RBCs and the drug loading amount was 0.84 ± 0.09 mg/mL. There was no significant change of particle size after surface modification of RBCs. The RBCs-based DDS could target to the surface of cancer cells, which delivery DOX to the lesions efficiently and accurately. Meanwhile, due to the combined treatment effect, the RBCs-based DDS can effectively inhibit tumor growth. The RBCs-based DDS constructed in this research may have promising applications in cancer therapy due to their highly synergistic efficient therapy and to investigate its possibility for tumor therapy.

Estrone-targeted liposomes for mitoxantrone delivery via estrogen receptor: In vivo targeting efficacy, antitumor activity, acute toxicity and pharmacokinetics

Estrogen receptor (ER) is a potential target receptor for ER-positive cancer therapy including breast cancers, gastric cancers, and human acute myeloblastic leukaemia. In order to reduce the side-effects of mitoxantrone (MTO), estrone-targeted liposomes for MTO delivery via ER were designed for selectively targeting cancer cells. In previous studies, MTO-loaded estrogen receptor targeted and sterically stabilized liposome (ES-SSL-MTO; ES: estrone, is known to bind the ER) had been synthesized and showed a very high antiproliferative effect with IC50 value of 0.7 ng/mL. Based on these, further studies including in vivo targeting efficacy and antitumor activity, acute toxicity and pharmacokinetics of MTO liposomes were carried out. The results showed SSL (sterically stabilized liposome, PEGylated liposome, PEG: Polyethylene Glycol) could reduce drug metabolism, improve the stability of liposomes, prolong in vivo circulation time of drugs, reduce the toxicity of MTO. But SSL could not be enriched in tumor tissues. However, estrone (ES)-targeted liposomes could be delivered to tumor sites. ES-SSL could effectively enter into ER-expressing tumor cellsand be accumulated, prolong the circulation time in vivo, reduce side effects of drug. ES-SSL-MTO could provide higher bioavailability than MTO, enhance the anti-tumor effect and the safety of MTO, reduce the toxicity and side effects of MTO and improve the therapeutic effect of MTO. These facts proved ES-SSL is a useful tumor-targeting drug delivery system for MTO.

Preparation of Isorhamnetin Nanoparticles and Their Targeting Efficiency to Nasopharynx Cancer.

Cancer is a serious threat to human health and longevity, and is an important cause of disease death. At present, cancer is mainly treated by surgery, radiotherapy, chemotherapy, etc. The existing various methods of treating tumors have their limitations. Although there are immune, genetic and other treatment methods, they are still immature. Therefore, tumor-targeted drug delivery systems have attracted more and more attention in cancer treatment. Targeted nano-drugs are selectively targeted to the tumor surface to achieve targeted drug delivery. New nano-drugs have created new hotspots in medical research. It could be a new strategy for treating cancer. Carboxymethyl chitosan (CMC) is formed by the carboxylation of chitosan. It has good water solubility and biodegradability, biocompatibility and antibacterial properties, so CMC is the best choice as a nanomaterial. Isorhamnetin (Iso) is an important anticancer drug. This article uses nanomedicine technology to construct CMC as a carrier, Iso as an antitumor drug, and using polydopamine (PDA) to modify the surface of the particles. Through in vitro and in vivo experiments, the Iso/CMC-PDA nanosphere Targeting and Growth Inhibition of Cervical Cancer Cells.

PH-sensitive β-cyclodextrin derivatives for the controlled release of Podophyllotoxin

An effective tumor targeting drug delivery systems was designed and synthesized by conjugating pH-sensitive maleamide derivatives to Mono-(6-deoxy-6-amino)-β-CD. Their characteristics and inclusion behaviors with insoluble anticancer drug PPT were investigated in both solution and solid state by means of 1H NMR and 2D-ROESY, XRD, DSC and SEM, which reveal PPT is successfully encapsulated in the cavity of CD derivatives with different stability constants (Ks). Water solubility of PPT are significantly increased to 60.35 and 22.89 mg·mL−1 after formation of inclusion complexes with host-1 and host-2, compared with free PPT (0.12 mg·mL−1). Their acid-controlled release has been studied in vitro by 1H NMR and UV-Vis spectra, living cells incubated with host 1-2 were observed by Inverted fluorescence microscope to confirm pH-response releasing. Moreover, host-1/PPT and host-2/PPT maintain effective cell proliferation inhibition to human cancer, while their cytotoxicity to normal cell is significantly reduced. Our work shows inspiring potential in tumor-targeted delivery and acid-controlled release of PPT both in vitro.