Anticancer Drug Delivery System Research Articles

Preparation and characterization of norcantharidin liposomes modified with stearyl glycyrrhetinate.

In the current study, norcantharidin (NCTD)-loaded liposomes (LIPs) modified with stearyl glycyrrhetinate (SG; SG-NCTD-LIP) were prepared by the ethanol injection method. To increase the drug encapsulation efficiency (EE), the formulation of NCTD-LIP was optimized by single factor test and orthogonal design. The release of NCTD in vitro from SG-NCTD-LIP was evaluated by equilibrium dialysis. The cytotoxicity of SG-NCTD-LIP in HepG2 was investigated by MTT assay. The results revealed that the EE of liposomes was ~27.80%, the average SG-NCTD-LIP was 87.5 nm, the in vitro NCTD release from SG-NCTD-LIP was delayed compared with NCTD in solution and the drug-release kinetic followed a first-order model. MTT assays revealed increased cytotoxicity activity against HepG2 cells for SG-NCTD-LIP compared with free NCTD. In conclusion, SG-NCTD-LIP prepared in the present study may be a promising liposomal drug delivery system for anticancer drugs in liver-targeting therapy.

Development of an Anticancer Therapy Using Recombinant Bifidobacterium as a New Drug Delivery System (DDS)

Intravenously administered obligate anaerobic bacteria, such as bifidobacteria, grow specifically in tumor tissues. This specificity is attributed to the following: (1) Vascular walls in tumor tissues have nanometer- to micrometer-wide cracks, which allow the bacteria to pass through; (2) the intratumoral environment is hypoxic, due to poor vascularization, and therefore bifidobacteria can survive and proliferate in this anaerobic environment; (3) bifidobacteria cannot survive in well-oxygenated normal tissues. Moreover, unlike gram-negative bacteria, the gram-positive bifidobacteria do not produce endotoxins; therefore, there is no risk of endotoxin shock associated with their intravenous administration. Recently, the utility of bifidobacteria for specific drug delivery to tumor tissues has been highlighted. We have established a novel anti-cancer drug-delivery system using Bifidobacterium longum for the specific release of anti-tumor antibodies (e.g., antibody-drug complexes or single-chain antibodies) to targeted tumor tissues. Here, we introduce the results of our investigation.

A Glutamine-Rich Carrier Efficiently Delivers Anti-CD47 siRNA Driven by a "Glutamine Trap" To Inhibit Lung Cancer Cell Growth.

It is not efficient enough using the current approaches for tumor-selective drug delivery based on the EPR effect and ligand-receptor interactions, and they have largely failed to translate into the clinic. Therefore, it is urgent to explore an enhanced strategy for effective delivery of anticancer agents. Clinically, many cancers require large amounts of glutamine for their continued growth and survival, resulting in circulating glutamine extraction by the tumor being much greater than that for any organs, behaving as a "glutamine trap". In the present study, we sought to elucidate whether the glutamine-trap effect could be exploited to deliver therapeutic agents to selectively kill cancer cells. Here, a macromolecular glutamine analogue, glutamine-functionalized branched polyethylenimine (GPI), was constructed as the carrier to deliver anti-CD47 siRNA for the blockage of CD47 "don't eat me" signals on cancer cells. The GPI/siRNA glutamine-rich polyplexes exhibited remarkably high levels of cellular uptake by glutamine-dependent lung cancer cells, wild-type A549 cells (A549WT), and its cisplatin-resistant cells (A549DDP), specifically under glutamine-depleted conditions. It was noted that the glutamine transporter ASCT2 was highly expressed both on A549WT and A549DDP but with almost no expression in normal human lung fibroblasts cells. Inhibition of ASCT2 significantly prevented the internalization of GPI polyplexes. These findings raised the intriguing possibility that the glutamine-rich GPI polyplexes utilize the ASCT2 pathway to selectively facilitate their cellular uptake by cancer cells. GPI further delivered anti-CD47 siRNA efficiently both in vitro and in vivo to downregulate the intratumoral mRNA and protein expression levels of CD47. CD47 functions as a "don't eat me" signal and binds to the immunoreceptor SIRPα inducing evasion of phagocytic clearance. GPI/anti-CD47 siRNA polyplexes achieved significant antitumor activities both on A549WT and A549DDP tumor-bearing nude mice. Notably, it had no adverse effect on CD47-expressing red blood cells and platelets, likely because of selective delivery. Therefore, the glutamine-rich carrier GPI driven by the glutamine-trap effect provides a promising new strategy for designing anticancer drug delivery systems.

Honokiol nanoparticles based on epigallocatechin gallate functionalized chitin to enhance therapeutic effects against liver cancer

This study aims to design a novel nano-sized anticancer drug delivery system that can enhance the therapeutic effects of the loaded drug. With this idea in mind, this work reported the design and characterization of epigallocatechin-3-gallate (EGCG) functionalized chitin (CH) derivative, and its application in nano-drug delivery system. The EGCG-functionalized CH (CE) polymer was firstly prepared and characterized. The nanoparticles (NPs) of CE-loaded honokiol (HK), which was prepared by ionic crosslinking, exhibited a size of 80 nm, zeta potential of +33.8 mV, and spherical morphology. The antitumor activity of the CE-HK NPs in vitro and in vivo was investigated and compared to free HK. As a result, the CE-HK NPs can effectively inhibited cell proliferation of HepG2 cell by inhibiting more cells in the G2/M phase and decreasing mitochondrial membrane potential. The CE-HK NPs (40 mg/kg) inhibited tumor growth by 83.55% (p < 0.05), which was far higher than the 30.15% inhibition of free HK (40 mg/kg). The proposed delivery system exhibits better tumor selectivity and growth reduction both in vitro and in vivo, and does not induce any side effects. Therefore, the CE-HK NPs may act as an effective delivery system of liver cancer agent HK.

Multi-functionalized chitosan nanoparticles for enhanced chemotherapy in lung cancer

Chemotherapy-based treatment for cancer has made great progress in the past decades. However, there is still a big challenge for the treatment of lung cancer. Herein, a multifunctional nanocarrier was developed through electrostatic interaction between the fluorescent gold nanocluster-conjugated chitosan and the nucleolin targeting AS1411 aptamer. Then methotrexate was loaded into the multifunctional nanocarrier through hydrophobic interaction to obtain the nanodrug carrier systems. The prepared nanodrug carrier systems have an average nanoparticle size of 200 nm with 13.8% drug loading efficiency. The drug release is pH-dependent. The in vitro results demonstrated that the nanodrug carrier systems were selectively taken up by cancer cells in a time-dependent manner and exhibited significantly enhanced anticancer activity in a model of lung cancer A549 cells. The in vivo results showed that intravenous administration of nanodrug carrier systems into BALB/c mice led to accumulation of methotrexate at the tumor site and significantly inhibited the tumor growth but without overt toxicity. The present study suggests that the prepared multifunctional nanocarrier can be used as an effective drug delivery system for anticancer drugs and exhibits great potential in clinical applications.

Enhanced Targeted Delivery of Doxorubicin Based on Acid Induced Charge Reversal and Combinational Stimuli‐Responsive Nanocarrier

To elevate the efficacy and to attenuate the adverse effects remain a tough challenge in exploring anticancer drug delivery systems. A nanocarrier characteristic of acid induced charge reversal and acid/redox/magnetic combinational stimuli‐responsiveness is designed. This system exhibits weaker repulsion between the carrier and the cancer cell membrane, resulting in enhanced uptake. After nanocarriers enter the cell, the system exhibits negative‐to‐positive charge reversal in response to the low intracellular pH value. Moreover, after the uptake, the carrier will be further dissociated by glutathione in cytoplasm via the reduction of the disulfide bond, leading to the rapid release of the encapsulated DOX into the nuclei. In vitro release study expresses the sequent stimulus release profile. The antitumor activity tested in CT26 tumor‐bearing mice reveals efficient therapeutic efficacy and as low adverse effect as PBS. H&amp;E staining and immunohistochemical analysis of tumor tissues as well as pathological test of tissue sections of vital organs confirm the high antitumor activity and low tissue toxicity. Thus, the belief that this system has a good prospect in the field of cancer clinical chemotherapy.

Synthesis and characterization of novel P(HEMA-LA-MADQUAT) micelles for co-delivery of methotrexate and Chrysin in combination cancer chemotherapy

A Novel poly [2-hydroxyethyl methacrylate-Lactide-dimethylaminoethyl methacrylate quaternary ammonium alkyl halide] [P(HEMA-LA-MADQUAT)] copolymer was synthesized through combination of ring opening polymerization (ROP) and ‘free’ radical initiated polymerization methods. This newly developed copolymer was fully characterized by FT-IR, 1HNMR and 13CNMR spectroscopy. Micellization of the copolymer was performed by dialysis membrane method and obtained micelles were characterized by FESEM, dynamic light scattering (DLS), zeta potential (ξ), and critical micelle concentration (CMC) measurements. This copolymer was developed with the aim of co-delivering two different anticancer drugs: methotrexate (MTX) and chrysin. In vitro cytotoxicity effect of MTX@Chrysin-loaded P(HEMA-LA-MADQUAT) was also studied through assessing the survival rate of breast cancer cell line (MCF-7) and DAPI staining assays. Cationic micelle (and surface charge of + 7.6) with spherical morphology and an average diameter of 55 nm and CMC of 0.023 gL−1 was successfully obtained. Micelles showed the drug loaded capacity around 87.6 and 86.5% for MTX and Chrysin, respectively. The cytotoxicity assay of a drug-free nanocarrier on MCF-7 cell lines indicated that this developed micelles were suitable nanocarriers for anticancer drugs. Furthermore, the MTX@Chrysin-loaded micelle had more efficient anticancer performance than free dual anticancer drugs (MTX @ chrysin), confirmed by MTT assay and DAPI stainingmethods. Therefore, we envision that this recently developed novel micelle can enhance the efficacy of chemotherapeutic agents, MTX and Chrysin, combination chemotherapy and has the potential to be used as an anticancer drug delivery system for in vivo studies. Therefore, this recently developed novel micelle can enhance the efficacy of chemotherapeutic agents, MTX and Chrysin, combination chemotherapy and has the potential to be used as an anticancer drug delivery system for in vivo studies.

Synthesis and properties of a biodegradable polymer-drug conjugate: Methotrexate-poly(glycerol adipate)

Polymer-drug conjugates have been actively developed as potential anticancer drug delivery systems. In this study, we report the first polymer-anticancer drug conjugate with poly(glycerol adipate) (PGA) through the successful conjugation of methotrexate (MTX). MTX-PGA conjugates were controllably and simply fabricated by carbodiimide-mediated coupling reaction with various high molar ratios of MTX. The MTX-PGA conjugate self-assembled into nanoparticles with size dependent on the amount of conjugated MTX and the pH of medium. Change in particle size was attributed to steric hindrance and bulkiness inside the nanoparticle core and dissociation of free functional groups of the drug. The MTX-PGA nanoparticles were physically stable in media with pH range of 5-9 and ionic strength of up to 0.15 M NaCl and further chemically stable against hydrolysis in pH 7.4 medium over 30 days but enzymatically degradable to release unchanged free drug. Although 30%MTX-PGA nanoparticles exhibited only slightly less potency than free MTX in 791T cells in contrast to previously reported human serum albumin-MTX conjugates which had >300 times lower potency than free MTX. However, the MTX nanoparticles showed 7 times higher toxicity to Saos-2 cells than MTX. Together with the enzymic degradation experiments, these results suggest that with a suitable biodegradable polymer a linker moiety is not a necessary component. These easily synthesised PGA drug conjugates lacking a linker moiety could therefore be an effective new pathway for development of polymer drug conjugates.

Polysialic acid-polyethylene glycol conjugate-modified liposomes as a targeted drug delivery system for epirubicin to enhance anticancer efficiency

Polysialic acid (PSA) is a nonimmunogenic and biodegradable polysaccharide. In recent years, PSA has shown its potential applications to cancer treatment. In this study, PSA-polyethylene glycol (PEG) conjugate was synthesized for the decoration of epirubicin (EPI)-loaded liposomes. The study aimed to evaluate the PSA-PEG conjugated modified liposomes (EPI-PSL) in vitro and in vivo to investigate the role of PSA on physicochemical characteristics and antitumor activity in PEGylated liposomes. EPI-PSL showed a particle size of 116.9 ± 5.2nm, zeta potential of - 40.3 ± 3.5mV, and encapsulation efficiency of 99.1 ± 1.5%. The results of in vitro release experiments showed a delayed release of EPI from EPI-PSL. Greater cellular uptake of EPI-PSL was observed compared with PEGylated liposomes (EPI-PL) in B16 cells. Cytotoxicity studies suggested that EPI-PSL exhibited stronger cytotoxic activity than EPI-PL. Though EPI-PSL exhibited comparable blood plasma profiles with EPI-PL, biodistribution studies proved that the distribution of EPI-PSL in tumors was more than that of EPI-PL. The superior antitumor efficacy of EPI-PSL was also verified in the B16 xenograft mouse model with a reduction in systemic toxicity. In conclusion, these results therefore indicated that PSA-modified PEGylated liposomes may represent an excellent anticancer drug delivery system for targeted cancer therapy.

In Vitro Characterization and Evaluation of the Cytotoxicity Effects of Nisin and Nisin-Loaded PLA-PEG-PLA Nanoparticles on Gastrointestinal (AGS and KYSE-30), Hepatic (HepG2) and Blood (K562) Cancer Cell Lines.

The aim of this study was an in vitro evaluation and comparison of the cytotoxic effects of free nisin and nisin-loaded PLA-PEG-PLA nanoparticles on gastrointestinal (AGS and KYSE-30), hepatic (HepG2), and blood (K562) cancer cell lines. To create this novel anti-cancer drug delivery system, the nanoparticles were synthesized and then loaded with nisin. Subsequently, their biocompatibility, ability to enter cells, and physicochemical properties, including formation, size, and shape, were studied using hemolysis, fluorescein isothiocyanate (FITC), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM), respectively. Then, its loading efficiency and release kinetics were examined to assess the potential impact of this formulation for the nanoparticle carrier candidacy. The cytotoxicities of nisin and nisin-loaded nanoparticles were evaluated by using the MTT and Neutral Red (NR) uptake assays. Detections of the apoptotic cells were done via Ethidium Bromide (EB)/Acridine Orange (AO) staining. The FTIR spectra, SEM images, and DLS graph confirmed the formations of the nanoparticles and nisin-loaded nanoparticles with spherical, distinct, and smooth surfaces and average sizes of 100 and 200nm, respectively. The loading efficiency of the latter nanoparticles was about 85-90%. The hemolysis test represented their non-cytotoxicities and the FITC images indicated their entrance inside the cells. An increase in the percentage of apoptotic cells was observed through EB/AO staining. These results demonstrated that nisin had a cytotoxic effect on AGS, KYSE-30, HepG2, and K562 cancer cell lines, while the cytotoxicity of nisin-loaded nanoparticles was more than that of the free nisin.

Doxorubicin loaded carboxymethyl cellulose/graphene quantum dot nanocomposite hydrogel films as a potential anticancer drug delivery system

Creating anticancer properties in the hydrogel film could make it as a candidate for treating cancer tissues. In this work, a novel hydrogel nanocomposite films with anticancer properties were designed via incorporation of graphene quantum dot (GQD) as a nanoparticle into carboxymethyl cellulose (CMC) hydrogel and using doxorubicin (DOX) as drug model with broad-spectrum anticancer properties. Drug release studies carried out at two different pHs and the MTT assay was evaluated for DOX-loaded CMC/GQD nanocomposite hydrogel films against blood cancer cells (K562). The prepared nanocomposite hydrogel films were characterized using Fourier transform infrared (FT-IR), UV–Vis spectroscopy, scanning electron microscopy (SEM), permeability and mechanical properties. The prepared CMC/GQD nanocomposite hydrogel films showed an improvement in vitro swelling, degradation, water vapor permeability and pH-sensitive drug delivery properties along with not significant toxicity against blood cancer cells (K562). According to the obtained results, this nanocomposite hydrogel films can be proposed to use as an anticancer film and drug delivery system.

Carrier-Free Microspheres of an Anti-Cancer Drug Synthesized via a Sodium Catalyst for Controlled-Release Drug Delivery.

There are several challenges involved in the development of effective anti-cancer drugs, including accurate drug delivery without toxic side effects. Possible systemic toxicity and the rapid biodegradation of drug carriers are potential risks in the use of carriers for drug-delivery formulations. Therefore, the carrier-free drug delivery of an anti-cancer drug is desirable. Herein, 4-amino-2-benzyl-6-methylpyrimidine (ABMP) was synthesized via a new method using a sodium catalyst, and proved to be effective in inducing breast cancer cell (MDA-MB-231) apoptosis. Moreover, the transparent amorphous state solid of ABMP was demonstrated to have a slow-release property in phosphate buffer solution (PBS). Microspheres of ABMP were prepared with diameters in the range of 5–15 μm. The slow-release property of the ABMP microspheres indicated their potential use for controlled-release drug delivery. We believe that microspheres of ABMP have potential as a new kind of carrier-free anti-cancer drug delivery system.

Synthesis of New Antibacterial Cubane-based Nanocomposite and its Application in Combination Cancer Therapy.

The need for therapeutically effective anticancer drug delivery systems constantly persuades researchers to explore novel strategies. In this study a novel cubane based antibacterial nanocomposite was tailored as dual chemotherapy drug delivery vesicle in order to increase the therapeutic outcome in cancer therapy. The physico-chemical characterization of engineered nanocarrier was assessed by Fourier transforms infrared spectroscopy (FTIR), Hydrogen nuclear magnetic resonance spectroscopy (1H NMR), Thermogravimetric analysis (TGA), and Field emission scanning electron microscopy-energy dispersive using X-ray (FESEMEDX). The antibacterial activity of novel developed nanocomposite was tested by determining minimum inhibitory concentration (MIC) values against Pseudomonas aeruginosa, Escherichia Coli and Candida albicans. In order to investigate the efficacy of novel engineered nanocomposite (with average particle size of 50 nm) as dual anticancer drug delivery, DOX and MTX were bind to nanocarrier with encapsulation efficiency and loading content of around 97.3 ± 2.7% and 20.8 ± 1.6 %, respectively. Dual drugs released simultaneously with distinct tumor targeted, pH responsive sustained release manner. Moreover, the probable antitumoral activity of this engineered nanocomposite system against MCF7 cell lines was evaluated by MTT assay and cell cycle studies. The outcomes showed that novel engineered nanocomposite had no cytotoxic effects, while DOX@MTX-loaded nanocomposite possessed higher growth inhibition property and higher S-phase arrest as compared to cells treated with DOX@MTX alone. It was concluded that this novel cubane based drug delivery vehicle could process antibacterial and anticancer therapeutics spontaneously, representing promising tumor targeted system in nanomedicine.

Self-sensibilized polymeric prodrug co-delivering MMP-9 shRNA plasmid for combined treatment of tumors

Polymeric prodrugs are of immense interest as anticancer drug-delivery system owing to their superior drug stability during circulation and satisfactory drug loading capacity. However, they are usually less effective than free drugs due to imperfect degradable characteristics or active sites blockage. A polymeric prodrug (HPAA-MTX) with chemotherapeutic self-sensibilization effect consisting of glutathione (GSH)-triggered hyperbranched poly(amido amine) (HPAA) and methotrexate (MTX) was designed and synthesized in this work. This prodrug not only showed better inhibition effect on the tumor cells proliferation compared with free MTX, but also displayed selective sensibilization to tumor cells rather than normal cells. Meanwhile, HPAA-MTX was also explored as a MMP-9 shRNA plasmid delivery vector due to their rich amino group of HPAA, accompanying with MTX for simultaneous inhibiting tumor cells proliferation and migration. As expected, HPAA-MTX possessed excellent gene delivery capacity with significant down-regulation expression of MMP-9 protein and further inhibition of MCF-7 cells migration. Benefiting from the self-sensibilization effect and MTX/MMP-9 co-delivery strategy, this HPAA-MTX/MMP-9 co-delivery system exhibited significantly improved therapeutic efficacy to breast cancer in a combined manner which was confirmed through in vitro and in vivo assays. The strategy established in this study provided a facile “all-in-one” platform to integrate the drug/gene co-delivery strategy and self-sensibilization effect into one single nanocomposite for potential cancer treatment. Statement of significanceA cationic polymeric prodrug with chemotherapeutic self-sensibilization effect was designed and showed better inhibition effect on tumor cells proliferation compared with its free drug, as well displayed the selective sensibilization effect to tumor cells rather than normal cells. Moreover, the prodrug could also deliver MMP-9 shRNA plasmid for a combined therapy. As expected, the prodrug possessed excellent gene delivery capacity with significant down-regulation expression of MMP-9 protein and further inhibition of MCF-7 cells migration. Benefiting from the self-sensibilization effect and the drug/gene co-delivery strategy, this prodrug exhibited significantly improved therapeutic efficacy to breast cancer in a combined manner.

Supramolecular Self-Assembled Nanogels a New Platform for Anticancer Drug Delivery.

Polymer micellar nanogels are a group of core-shell polymeric micelles with swelling properties in aqueous media. Nanogel systems have proven their potential in controlled, sustained and targetable drug delivery area with no immunological responses. This review includes a comprehensive wide range of self-assembly of polymeric nanogels as delivery systems for anticancer drugs. Nanogels are nanoparticulate drug delivery systems which are specially designed for enhanced target oriented and cellular uptake of drugs with emphasis on chemotherapeutic agents studied in this review. Self-assembling nanogels are based on natural substances or synthetic polymers including: hyaluronic acid, heparin, alginate, cyclodextrins, chondroeitin sulfate, starch, mannan, chitosan, pullulan, poly(N-isopropylacrylamide), polyvynil alcohol, Pluronic F127, polyacrylic acid, poly(hydroxylethyl methacrylate), poly[2- (dimethylamino)ethyl methacrylate and polylactide-co-glycolide-polyethylen glycol amphiphilic di or tri block copolymer used to deliver anticancer drugs are introduced and discussed.

Self-Assembled Nanocarriers Based on Amphiphilic Natural Polymers for Anti- Cancer Drug Delivery Applications.

Micellization provides numerous merits for the delivery of water insoluble anti-cancer therapeutic agents including a nanosized 'core-shell' drug delivery system. Recently, hydrophobically-modified polysaccharides and proteins are attracting much attention as micelle forming polymers to entrap poorly soluble anti-cancer drugs. By virtue of their small size, the self-assembled micelles can passively target tumor tissues via enhanced permeation and retention effect (EPR). Moreover, the amphiphilic micelles can be exploited for active-targeted drug delivery by attaching specific targeting ligands to the outer micellar hydrophilic surface. Here, we review the conjugation techniques, drug loading methods, physicochemical characteristics of the most important amphiphilic polysaccharides and proteins used as anti-cancer drug delivery systems. Attention focuses on the mechanisms of tumor-targeting and enhanced anti-tumor efficacy of the encapsulated drugs. This review will highlight the remarkable advances of hydrophobized polysaccharide and protein micelles and their potential applications as anti-cancer drug delivery nanosystems. Micellar nanocarriers fabricated from amphiphilic natural polymers hold great promise as vehicles for anti-cancer drugs.

PH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery.

BackgroundAnticancer drug-delivery systems (DDSs) capable of responding to the physiological stimuli and efficiently releasing drugs inside tumor cells are highly desirable for effective cancer therapy. Herein, pH-responsive, charge-reversal poly(allylamine hydrochlorid)−citraconic anhydride (PAH-cit) functionalized boron nitride nanospheres (BNNS) were fabricated and used as a carrier for the delivery and controlled release of doxorubicin (DOX) into cancer cells.MethodsBNNS was synthesized through a chemical vapor deposition method and then functionalized with synthesized charge-reversal PAH-cit polymer. DOX@PAH-cit–BNNS complexes were prepared via step-by-step electrostatic interactions and were fully characterized. The cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release inside cancer cells were visualized by confocal laser scanning microscopy. The in vitro anticancer activity of DOX@ PAH-cit–BNNS was examined using CCK-8 and live/dead viability/cytotoxicity assay.ResultsThe PAH-cit–BNNS complexes were nontoxic to normal and cancer cells up to a concentration of 100 µg/mL. DOX was loaded on PAH-cit–BNNS complexes with high efficiency. In a neutral environment, the DOX@PAH-cit–BNNS was stable, whereas the loaded DOX was effectively released from these complexes at low pH condition due to amide hydrolysis of PAH-cit. Enhanced cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release in the nucleus of cancer cells were revealed by confocal microscopy. Additionally, the effective delivery and release of DOX into the nucleus of cancer cells led to high therapeutic efficiency.ConclusionOur findings indicated that the newly developed PAH-cit–BNNS complexes are promising as an efficient pH-responsive DDS for cancer therapy.

2D-BN nanoparticles as a spectroscopic marker and drug delivery system with protection properties.

An application of 2D-BN nanoparticles as a spectroscopic marker, weak luminescent marker and anticancer drug (doxorubicin, DOX) delivery system with protection properties was studied for the LNCaP strains of cancer cells using FTIR and Raman spectroscopy for analysing the cancer cells, cells with BN, the cancer cells with DOX, and the cancer cells with BN nanoparticles loaded by DOX. Study of IR absorption and Raman spectra of the LNCaP strains of cancer cells incubated with 2D-BN nanoparticles for 1 hour showed that the 2D-BN nanoparticles could pass through the cell membrane and localize inside the membrane or close to the membrane in the cytoplasm of the cells. We registered the spectra of the disturbed lipids during the DOX-2D-BN passing through the membrane. After incubation for 2 hours and more, spectral changes in other structural components of the cell (nuclei, cytoplasm, mitochondria) can be registered. Confocal microscopy showed that a gold nanostructured support enhances the fluorescence of the cancer cells with 2D-BN as well as that with DOX, however the double action of 2D-BN and DOX on the cancer cells aggravates the emission property of the studied system. An MTT test showed that the toxicity of DOX on the 2D-BN nanoparticles is less than that on the reference cells, and at the same time the efficiency of the DOX action on the cancer cells does not change.

L-Peptide functionalized dual-responsive nanoparticles for controlled paclitaxel release and enhanced apoptosis in breast cancer cells

Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5%) and excellent encapsulation efficiency (74.3%) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid – and thermally activated – PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.

An Adeninate-Based Metal–Organic Framework for Antitumour Drug Delivery and Anti-Osteogenic Sarcoma Activity Evolution

Targeted anticancer drug delivery systems (DDSs) have been considered as one of the most important approaches for reducing the side effects and enhancing the therapy effect in cancer treatment. This work presents a targeted anticancer DDS on the basis of a newly synthesised adeninate-based metal–organic framework (MOF) [Zn2(ad)2(AMDB)(H2O)](DMF)3 (1) with biomolecular adenine (HAd), zinc(ii) ions, and 4,4′-(aminomethylene)dibenzoic acid (H2AMDB) as the molecular building blocks. The structural analysis via X-ray diffraction technology shows MOF 1 is a channel-type three-dimensional network composed of rod-like Zn–Ad chains. Due to its large inner free spaces and uncoordinated N donor sites functionalised pore surroundings, the antitumour molecule 5-fluorouracil (5-Fu) could be loaded into the pores of 1a (activated 1) though an adsorption process, which shows a moderate high storage capacity of 32 wt-%. At the same time, the pH-dependent delivery of 5-Fu could be achieved in phosphate-buffered saline (PBS) solution. With a lower pH value, the drug release will be enhanced. Furthermore, the invitro antitumour activity of the drug/1a composite has been probed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on two human osteogenic sarcoma cells (MG63 and U2OS).