Cisplatin-Based Combination Therapy for Enhanced Cancer Treatment.

Cisplatin, a primary chemotherapeutic drug, is of great value in the realm of tumor treatment. However, its clinical efficacy is strictly hindered by issues, such as drug resistance, relapse, poor prognosis, and toxicity to normal tissue. Cisplatin-based combination therapy has garnered increasing attention in both preclinical and clinical cancer research for its ability to overcome resistance, reduce toxicity, and enhance anticancer effects. This review examines three primary co-administration strategies of cisplatin-based drug combinations and their respective advantages and disadvantages. Additionally, seven types of combination therapies involving cisplatin are discussed, focusing on their main therapeutic effects, mechanisms in preclinical research, and clinical applications. This review also discusses future prospects and challenges, aiming to offer guidance for the development of optimal cisplatin-based combination therapy regimens for improved cancer treatment.

Functions and targets of miRNAs in pharmacological and toxicological effects of major components of Tripterygium wilfordii Hook F.

Tripterygium wilfordii Hook F (TwHF) has a long history of use as a traditional Chinese medicine and has been widely administered to treat various inflammatory and autoimmune diseases. MicroRNAs (miRNAs) are endogenous, short, non-coding RNAs that regulate gene expression post-transcriptionally. They participate in the efficacies and even toxicities of the components of TwHF, rendering miRNAs an appealing therapeutic strategy. This review summarizes the recent literature related to the roles and mechanisms of miRNAs in the pharmacological and toxicological effects of main components of TwHF, focusing on two active compounds, triptolide (TP) and celastrol (CEL). Additionally, the prospects for the "You Gu Wu Yun" theory regarding TwHF nephrotoxicity are presented.

A smartphone-integrated portable platform based on polychromatic ratiometric fluorescent paper sensors for visual quantitative determination of norfloxacin.

The emergence of "superbugs" due to antibiotics overuse poses a significant threat to human health and security. The development of sensitive and effective antibiotics detection is undoubtedly a prerequisite for addressing antibiotics overuse-associated issues. However, current techniques for monitoring antibiotics typically require costly equipment and well-trained professionals. Hence, we developed herein a rapid, instrument-free, and on-site detection method for antibiotic residues such as norfloxacin (NOR) based on a ratiometric sensing platform utilizing "on-off-on" response properties of polychromatic fluorescence for direct visual quantitative NOR analysis. Specifically, this platform integrated iron ions (Fe3+)-chelated blue carbon dots (BCDs) for signal sensing and red carbon dots (RCDs) as an internal reference. The sensor mechanism is selective quenching of BCDs' blue fluorescence by Fe3+ via an inner filter effect with unaffected RCDs' red fluorescence. Further NOR addition led to competitive binding with BCDs due to Fe3+ shedding from the BCDs' surface for a recovered blue fluorescence signal. Notably, the ratiometric fluorescence sensor demonstrated rapid and highly sensitive NOR detection in a concentration range of 1-70 µM with an impressive detection limit of 6.84 nM. The ratiometric fluorescence sensing platform was constructed by integrating smartphone and paper-based strategies, which exhibited exceptional sensitivity, selectivity, and rapid response for portable, instrument-free, visual quantification of NOR in real samples.

A Sodium Alginate-Based Multifunctional Nanoplatform for Synergistic Chemo-Immunotherapy of Hepatocellular Carcinoma.

Efficient hepatocellular carcinoma (HCC) treatment remains a significant challenge due to the inherent limitations of traditional strategies. The exploration of polysaccharides' natural immunity for HCC immunotherapy is rarely explored. For this purpose, facile construction of a multifunctional nanoplatform, biotinylated aldehyde alginate-doxorubicin nano micelle (BEACNDOXM) is reported in this study for synergistic chemo-immunotherapy by using constant ß-D-mannuronic acid (M) units and modulated α-L-guluronic acid (G) units in the alginate (ALG) structure. The M units show natural immunity and specific binding ability with mannose receptors (MRs) via strong receptor-ligand interactions, and the G units serve as highly reactive conjugation sites for biotin (Bio) and DOX. Therefore, this formulation not only integrates the natural immunity of ALG and the immunogenic cell death (ICD) triggering function of DOX, but also shows dual targeting properties to HCC cells via MRs and Bio receptors (BRs)-mediated endocytosis. Notably, BEACNDOXM mediates a tumor inhibitory efficiency 12.10% and 4.70% higher than free DOX and single targeting aldehyde alginate-doxorubicin nano micelle controls, respectively, at an equivalent DOX dose of 3 mg kg-1 in Hepa1-6 tumor-bearing mice. This study reports the first example of integrating the natural immunity of ALG and the ICD effect of anticancer drugs for enhanced chemo-immunotherapy of HCC.

A Clinically Translatable Ternary Platinum(IV) Prodrug for Synergistically Reversing Drug Resistance  .

Scalable production of a clinically translatable formulation with enhanced therapeutic efficacy against cisplatin-resistant tumors without the use of any clinically unapproved reagents and additional manipulation remains a challenge. For this purpose, we report herein the construction of TPP-Pt-acetal-CA based on all commercially available, clinically approved reagents consisting of a cinnamaldehyde (CA) unit for reactive oxygen species generation, a mitochondrially targeted triphenylphosphonium (TPP)-modified Pt(IV) moiety for mitochondrial dysfunction, and an intracellular acidic pH-cleavable acetal link between these two moieties. The resulting self-assembled, stabilized TPP-Pt-acetal-CA nanoparticles mediated an IC50 value approximately 6-fold lower than that of cisplatin in A549/DDP cells and a tumor weight reduction 3.6-fold greater than that of cisplatin in A549/DDP tumor-bearing BALB/c mice with insignificant systematic toxicity due to the synergistic mitochondrial dysfunction and markedly amplified oxidative stress. Therefore, this study presents the first example of a clinically translatable Pt(IV) prodrug with enhanced efficiency for synergistically reversing drug resistance.

Pd-Pt-Ru nanozyme with peroxidase-like activity for the detection of total antioxidant capacity.

The design of highly active nanozymes and the establishment of ultra-sensitive bioassays remain a challenge. Therefore, it is necessary to synthesize highly active nanozymes. In this work, a Pd-Pt-Ru (PPR) nanozyme was prepared by atomic coating of the bimetallic nanozyme Pd-Pt. The steady-state kinetics showed that the PPR nanozyme had excellent peroxidase-like activity. Based on this concept, the as-prepared PPR nanozyme was applied to the detection of ascorbic acid (AA) and hydrogen peroxide (H2O2). The linear ranges for ascorbic acid and hydrogen peroxide were 2-12 µM and 5-40 mM, respectively. The limits of detection (LOD) are 1.13 µM and 2.79 mM, respectively. Ascorbic acid was used as a typical model to assay the total antioxidant capacity (TAC) of foods and several herbs. The Fructus Corni extract showed the highest reducing ability. The corresponding extracts were applied for the green synthesis of silver nanoparticles with a size of 167 nm. This study provides a method for the design of highly active nanozymes and the expansion of their applications.

Prolonged blood circulation outperforms active targeting for nanocarriers-mediated enhanced hepatocellular carcinoma therapy in vivo.

Successful hepatocellular carcinoma (HCC) therapy in vivo remains a significant challenge due to the down-regulated expression of the receptors on the surface of tumor cells for compromised active targeting efficiency and cellular uptake of nanoparticles (NPs)-based drug delivery systems (DDSs) and "accelerated blood clearance" and premature unpackaging of NPs in vivo induced by the poly(ethylene glycol)ylation (PEGylation). Inspired by the repeatedly highlighted prolonged blood circulation property of RBCm-camouflaged NPs, we hypothesis that the prolonged blood circulation property resulting from RBCm coating outperforms the active targeting mechanisms of various targeting ligands for enhanced HCC therapy in vivo. Clarification of this hypothesis is therefore of great significance and urgency to break the afore mentioned bottlenecks that hamper the efficient HCC treatment in vivo. For this purpose, we reported in this study the first identification of a determining factor of nanocarriers for enhanced HCC therapy in vivo by the use of the previously fabricated pectin-doxorubicin nanoparticles (PDC-NPs) as a typical example, i.e., the natural RBCm was used as a stealth coating of PDC-NPs for the fabrication of biomimetic DDSs, PDC@RBC-NPs via hypotonic dialysis and mechanical co-extrusion methods. Comprehensive in vitro and in vivo evaluation and comparison of the properties and performance of PDC@RBC-NPs and PDC-NPs were performed in terms of colloidal stability, biosafety, drug release profiles, macrophage escape, anti-HCC effect. The resulting PDC@RBC-NPs outperformed PDC-NPs for HCC therapy in vitro and in vivo. Notably, PDC@RBC-NPs-treated BALB/c nude mice showed a significantly smaller final average tumor volume of 613 mm3 after 16 days than the PDC-NPs-treated group with an average value of 957 mm3. Therefore, the PDC@RBC-NPs developed herein showed great potential for clinical transformations due to the facile preparation and superior therapeutic efficiency against HCC. Most importantly, prolonged blood circulation was identified as a determining factor of nanocarriers instead of active targeting for enhanced HCC therapy in vivo, which could be used to direct the future design and development of advanced DDSs with greater therapeutic efficiency for HCC.

Functionalized PAMAM-based Nanoformulation for Targeted Delivery of 5-Fluorouracil in Hepatocellular Carcinoma.

BACKGROUND: The efficacy of a traditional anticancer drug is challenged by adverse effects of the drug, including its nonspecific bio-distribution, short half-life, and side effects. Dendrimer-based targeted drug delivery system has been considered a promising strategy to increase targeting ability and reduce adverse effects of anti-cancer drugs. OBJECTIVE: This study analyzed the feasibility of whether the anticancer drug 5-fluorouracil (5-FU) could be delivered by functionalized fifth-poly(amidoamine) (PAMAM) with the peptide WP05 and the acetic anhydride to the liver cancer cells, reducing the toxicity of the PAMAM and improving the targeting property of 5-FU during delivery. METHODS: The functionalized PAMAM-based nanoformulation (WP05-G5.0NHAC-FUA) was fabricated through an amide condensation reaction to improve the therapeutic efficacy of 5-Fluorouracil (5-FU) in hepatocellular carcinoma (HCC). The physicochemical structure, particle size, zeta potential, stability, and in vitro release characteristics of WP05-G5.0NHAC-FUA were evaluated. In addition, the targeting, biocompatibility, anti-proliferation, and anti-migration of WP05-G5.0NHAC-FUA were investigated. The anti-tumor effect of WP05-G5.0NHAC-FUA in vivo was evaluated by constructing xenograft tumor models of human hepatoma cells (Bel-7402) implanted in nude mice. RESULTS: The resultant WP05-G5.0NHAC-FUA displayed spherical-like nanoparticles with a size of 174.20 ± 3.59 nm. Zeta potential and the drug loading of WP05-G5.0NHAC-FUA were 5.62 ± 0.41mV and 28.67 ± 1.25%, respectively. Notably, the optimized 5-FU-loaded formulation showed greater cytotoxicity with an IC50 of 30.80 ± 4.04 µg/mL than free 5-FU (114.93 ± 1.43 µg/mL) in Bel-7402 cancer liver cells, but a significantly reduced side effect relative to free 5-FU in L02 normal liver cells. In vivo animal study further confirmed efficient tumor accumulation and enhanced therapeutic efficiency. CONCLUSION: The developed nanoformulation is a promising platform for the targeting delivery of 5-FU and provides a promising solution for improving the efficacy of hepatocellular carcinoma chemotherapy.

Two-dimensional colloidal crystal of soft microgel spheres: Development, preparation and applications.

Two-dimensional (2D) colloidal crystals are ordered monolayer arrays of colloidal sphere particles assembled on the substrates or at phase interfaces. Owing to their unique periodic structure and fascinating properties, 2D colloidal crystals have aroused considerable interest because of their potential applications. Among them, 2D colloidal crystals self-assembled from soft microgel spheres stand out particularly. The 2D colloidal crystals of soft microgel spheres combine the advantages of monolayer colloidal crystals and sensitive microgels, which have a good application prospect in biomedical area. In this article, we provide a systematic overview of 2D colloidal crystals of soft microgel spheres related to their development, preparation and applications. First, various preparation methods of 2D colloidal crystal of microgels are introduced, including dip-coating, drop-coating, spin-coating, interface assembly, surface reaction-assisted assembly, and so forth. Second, representative biomedical applications consisting of optical sensor, drug delivery, antibacterial coating, cell culture, and colloidal template are also exemplified to show the high performance of 2D colloidal crystals of soft microgel spheres. In addition, we also present prospects of future developments of 2D microgel colloidal crystals.

NIR-to-Vis Handheld Platforms for Detecting miRNA Level and Mutation Based on Sub-10 nm Sulfide Nanodots and HCR Amplification.

Sub-10 nm monodisperse alkaline-earth sulfide nanodots (ASNDs) with bright near-infrared (NIR)-excitation fluorescence and adjustable emission wavelength were prepared by a thermal decomposition method for the first time. The ASNDs exhibited high NIR-to-vis conversion efficiency and served as multicolor fluorescent labels in the proposed miR-224 assay. Targeted detection of the miR-224 level and single-nucleotide variation in miR-224 was carried out on a smartphone-based platform using a hybridization chain reaction (HCR) amplification strategy. In the presence of miR-224, the ASND-labeled HCR probes self-assembled on the surface of the diagnosis kits, generating strong fluorescent signals linearly proportional to miR-224 contents in the range of 10-2000 fM. Significantly, mutations in miR-224 led to the variation in the fluorescence intensity ratio in RGB channels. Simultaneously, evident changes of fluorescent brightness and color were easily visualized by the naked eye, which enabled on-site discrimination of miR-224 with different mutant loci. This work provides a novel preparation approach for ultrasmall NIR excitation sulfide nanodots and reveals the potential of the as-synthesized ASNDs in point-of-care (POC) nucleic acid testing. Further, it may provide a handheld platform for miRNA single-nucleotide polymorphism analysis.

Design, synthesis, and biological evaluation of 3',4',5'-trimethoxy evodiamine derivatives as potential antitumor agents.

A series of compounds bearing 3',4',5'-trimethoxy module into the core structure of evodiamine were designed and synthesized. The synthesized compounds were screened in vitro for their antitumor potential. MTT results showed that compounds 14a-14c and 14i-14j had significant effects, with compound 14h being the most prominent, with an IC50 value of 3.3 ± 1.5 µM, which was lower than evodiamine and 5-Fu. Subsequent experiments further confirmed that compound 14h could inhibit cell proliferation and migration, and induce G2/M phase arrest to inhibit the proliferation of HGC-27 cells, which is consistent with the results of the cytotoxicity experiment. Besides, 14h could inhibit microtubule assembly and might kill tumor cells by inhibiting VEGF and glycolysis. All experimental results indicate that compound 14h might be a potential drug candidate for the treatment of gastric cancer and was worthy of further study.

Facile Fabrication of Nanoparticles with Dual-Targeting Ligands for Precise Hepatocellular Carcinoma Therapy In Vitro and In Vivo.

Efficient hepatocellular carcinoma (HCC) therapy remains a significant challenge due to the unsatisfactory targeting efficiency of nanoparticles (NPs) with either a passive targeting or a single active targeting property. Although a dual-targeting mechanism-based strategy can promote the partial targeting efficiency, most of the reported NPs with dual-targeting properties generally suffer from sophisticated chemical design, multistep synthesis, and purification procedures, leading to batch-to-batch variation and difficulties in scalable production. To develop a facile yet efficient strategy toward dual-targeting ligand-functionalized NPs for precise HCC therapy and potential clinical translation, folic acid (FA) was readily introduced as a hydrophobic and targeting component to a hydrophilic macromolecular prodrug, galactosylated chitosan-5-fluorouracil acetic acid (GC-FU), to afford FA-GC-FU formulation that can self-assemble into NPs driven by the solubility variation of FA and GC-FU without the necessity of previously used physical cross-linking. The resulting nanoparticles of FA-GC-FU can target the overexpressed asialoglycoprotein receptors (ASGPRs) and folate receptors (FRs) on the surface of HCC cells, respectively, via the FA and lactobionic acid (LA) residues exposed on the surface of the NPs, leading to the maximized targeting efficiency of HCC and minimized nonspecific uptake by normal hepatocytes in vitro and in vivo. Therefore, this study not only developed a simple yet efficient strategy toward a facile fabrication of NPs with dual-targeting ligands but also presented a precise therapeutic platform for HCC with great potential for clinical translation.

Cell membrane-camouflaged nanoparticles as drug carriers for cancer therapy.

The translocation of natural cell membranes to the surface of synthetic nanoparticles, which allows man-made vectors to share merits and functionalities created by nature, has been a hot subject of research in the past decade. The resulting biomimetic nanoparticles not only retain the physicochemical properties of nanomaterials, but also inherit the advantageous functions of source cells. Combined with the preponderances of both synthetic and natural platforms, the optimized biomimetic systems can maximize the drug delivery efficiency. In this review, we first summarize the preparation strategies of the biomimetic systems from the perspective of the correlation between the properties of nanoparticles and cell membranes. Six types of cell membrane-camouflaged nanoparticles are further introduced with an emphasis on their properties and performance. Finally, a concluding remark regarding the primary challenges and opportunities associated with these nanoparticles is presented. STATEMENT OF SIGNIFICANCE: Translocation of natural cell membranes to the surface of synthetic nanoparticles has been repeatedly highlighted in the past decade to endow man-made vectors with merits and functionalities created by nature; therefore, the resulting biomimetic systems not only retain the physicochemical properties of nanomaterials but also inherit the biological functions of source cells for efficient drug delivery. To provide a timely review on this hot and rapidly developing subject of research, this paper summarized recent progress on the cell membrane-camouflaged nanoparticles as drug carriers for cancer therapy, and focused primarily on six different types of cell membrane-coated nanoparticles with an emphasis on the preparation strategies from the perspective of the correlation between the properties of nanoparticles and cell membrane.

MicroRNA-based potential diagnostic, prognostic and therapeutic applications in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a distinct subtype of breast cancer characterized by high recurrence rates and poor prognosis compared to other breast cancers. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of various post-transcriptional gene and silence a broad set of target genes. Many recent studies have demonstrated that miRNAs play an important role in the initiation, promotion, malignant conversion, progression, and metastasis of TNBC. Therefore, the aim of this review is to focus on recent advancements of microRNAs-based potential applications in diagnosis, treatment and prognosis of triple-negative breast cancer.

Design, synthesis and biological evaluation of tryptamine salicylic acid derivatives as potential antitumor agents.

A series of tryptamine salicylic acid derivatives were synthesized and their antiproliferative activity against MGC-803, MCF-7, HepG2, A549 and HeLa cell lines was evaluated. The structure-activity relationship (SAR) study revealed that different substitutions of the C5 and C3'-C5' positions have certain effects on the anti-proliferation activity. The growth assay revealed that N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide (E20) showed the most potent and broad-spectrum anticancer inhibition of all the cell lines evaluated, and was only more potent than 5-Fu for the gastric cancer cell line. Preliminary studies indicated that compound E20 could inhibit colony formation and migration of MGC-803 cells. The flow cytometry (FCM) results showed that compound E20 arrested the cell cycle in the G2/M phase and induced apoptosis of MGC-803 cells in a concentration-dependent manner. In addition, the western blot results showed that E20 can down-regulate the expression of hexokinase 2. Our studies suggest that the framework of N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide may be consider as a new type of chemical for designing effective anti-cancer drugs targeting gastric cancer cells.

Delivery of Liver-Specific miRNA-122 Using a Targeted Macromolecular Prodrug toward Synergistic Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) poses a great threat to human health. The elegant combination of gene therapy and chemotherapy by nanocarriers has been repeatedly highlighted to realize enhanced therapeutic efficacy relative to monotreatment. However, the leading strategy to achieve the efficient codelivery of the gene and drug remains the electrostatic condensation with the nucleic acid and the hydrophobic encapsulation of drug molecules by the nanocarriers, which suffers substantially from premature drug leakage during circulation and severe off-target-associated side effects. To address these issues, we reported in this study the codelivery of liver-specific miRNA-122 and anti-cancer drug 5-fluorouracil (5-Fu) using a macromolecular prodrug approach, that is, electrostatic condensation with miRNA-122 using galactosylated-chitosan-5-fluorouracil (GC-FU). The delivery efficacy was evaluated comprehensively in vitro and in vivo. Specifically, the biocompatibility of GC-FU/miR-122 nanoparticles (NPs) was assessed by hemolysis activity analysis, BSA adsorption test, and cell viability assay in both normal liver cells (L02 cells) and endothelial cells. The resulting codelivery systems showed enhanced blood and salt stability, efficient proliferation inhibition of HCC cells, and further induction apoptosis of HCC cells, as well as downregulated expression of ADAM17 and Bcl-2. The strategy developed herein is thus a highly promising platform for an effective codelivery of miRNA-122 and 5-Fu with facile fabrication and great potential for the clinical translation toward HCC synergistic therapy.

Facile fabrication of a novel hybrid nanoparticles by self-assembling based on pectin-doxorubicin conjugates for hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is one of the greatest public health problems worldwide, and chemotherapy remains the major approach for the HCC treatment. Doxorubicin (DOX) is one of the anthracycline antibiotics but its clinical use is limited due to its severe cardiotoxicity. In this study, novel hybrid nanoparticles by self-assembling based on pectin-doxorubicin conjugates (PDC-NPs) were fabricated for HCC treatment. The stabilized structure of the PDC-NPs was characterized by methylene blue absorption, the size, zeta potential and the morphology, which was investigated by Zetasizer nanoparticle analyzer and transmission electron microscope (TEM), of nanoparticles. The PDC-NPs achieved a sustained and prolonged release ability, which was illustrated with in vitro drug release profiles, anti-cell proliferation study, cellular uptake assay and in vivo pharmacokinetics analysis. Biocompatibility of the PDC-NPs was assessed with bovine serum albumin (BSA) adsorption test, hemolysis activity examination and viability evaluation of human umbilical vein endothelial cells. Importantly, in vivo studies of the PDC-NPs, which were performed in the athymic BALB/c nude mice, demonstrated that the PDC-NPs significantly reduced the lethal side effect of DOX. Additionally, the H&E staining and serum biochemistry study further confirmed the excellent biological security of the PDC-NPs.

Fabrication and characterization of a novel self-assembling micelle based on chitosan cross-linked pectin-doxorubicin conjugates macromolecular pro-drug for targeted cancer therapy.

Cancer is one of the leading causes of morbidity and mortality worldwide. Doxorubicin is one of the most effective anticancer drugs approved by FDA. However, like all the other anticancer drugs, the efficacy of DOX is associated with high systemic toxicity to healthy tissues. In this study, chitosan cross-linked pectin-doxorubicin conjugates macromolecular pro-drug (CS-PDC-M) was prepared to enhance the therapeutic effects on liver cancer. CS-PDC-M was characterized in terms of size, size distribution, zeta potential, scanning electron microscope (SEM) and drug loading content. The CS-PDC-M achieved prolonged releasing ability was demonstrated by the in vitro drug release and in vitro cellular uptake assay. Biocompatibility of CS-PDC-M was screened by hemolysis activity examination, BSA adsorption test and cell viability evaluation in endothelial cells and LO2 cells. The CS-PDC-M achieved significantly high antitumor efficiency and targeting efficiency, which was demonstrated by the in vitro MTT assay and cellular targeting assay toward HepG2 cells, MCF-7 cells and A549 cells. The in vivo antitumor efficacy of CS-PDC-M was studied in athymic BALB/c nude mice bearing HepG2 cell xenografts. The organ damage assays of CS-PDC-M was studied in SD rats. Compared with that of free DOX and PDC-M, the CS-PDC-M exhibited higher antitumor efficacy and lower toxicity, implying that CS-PDC-M is a highly promising drug delivery system for hepatocellular carcinoma treatment.

Fabrication and characterization of a folic acid-bound 5-fluorouracil loaded quantum dot system for hepatocellular carcinoma targeted therapy.

In the present study, we covalently coupled folic acid (FA) and 5-fluorouracil acetic acid (FUA) on the surface of quantum dots (QDs) to produce a tumor targeting drug delivery system, FA-QDs-FUA. The QDs not only act as hepatocellular carcinoma (HCC)-targeted delivery vehicles, but also play a key role in imaging. The structural and optical properties of as-prepared FA-QDs-FUA were characterized using UV-visible spectra, fluorescence spectra, infrared spectra, particle size and zeta potential. In vitro hemolysis activity, cytotoxicity and targeting specificity of the FA-QDs-FUA system were also evaluated. The in vivo anti-tumor efficacy of FA-QDs-FUA in tumor-bearing mice was investigated. The average particle size and zeta potential of FA-QDs-FUA was 220.28 nm and -13.3 mV, respectively. The drug-loading content of FA-QDs-FUA was 36.85% ± 1.61% (n = 3). The in vitro release profile of 5-FU from FA-QDs-FUA demonstrated a slow and sustained release behaviour as compared to free 5-FU drug. The results of the in vitro cellular experiment demonstrated that FA-QDs-FUA reduced cytotoxicity as compared to free 5-FU and targeted more easily hepatocellular carcinoma cells (SMMC-7721 and HepG2) than normal cells. Mice treated with FA-QDs-FUA showed superior tumor suppression compared to those treated with free 5-FU at 4.72 mg kg-1 of 5-FU. Therefore, the FA-QDs-FUA system can be used as a promising candidate for improving 5-FU efficacy and tumor targeting specificity with limited toxicity.

In vitro and in vivo evaluation of macromolecular prodrug GC-FUA based nanoparticle for hepatocellular carcinoma chemotherapy.

A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface. Pharmacokinetics study further illustrated that the drug-loaded nanoparticles has a much longer half-time than free 5-Fu in blood circulation in Sprague-Dawley (SD) rats. Tissue distribution was investigated in Kunming mice, and the result showed that the GC-FUA-NPs have a long circulation effect. The obtained data suggested that GC-FUA-NP is a very promising drug delivery system for efficient treatment of hepatocellular carcinoma.