Side Effects Of Anticancer Drugs Research Articles

Novel selective anticancer agents based on Sn and Au complexes. Mini-review

Abstract Cancer is one of the most common causes of death in modern medicine. Molecular design of novel substances with pharmacological activity is one of the goals of medicinal inorganic chemistry. Platinum complexes are widely used in the treatment of cancer, despite high efficacy their use is limited by side effects, as well as primary or acquired resistance. In this regard, the search for novel metal-containing antitumor compounds is underway. Organotins and gold compounds are promising pharmacological agents with anti-cancer properties. The introduction of protective antioxidant fragments into inorganic compounds molecules is a way to reduce the side effects of anti-cancer drugs on healthy cells. 2,6-dialkylphenols belonging to vitamin E (α-tocopherol) mimetics are widely used as antioxidants and stabilizers. The properties of Ph3SnCl (Sn-I), Ph3PAuCl (Au-I) and complexes Ph3SnSR (Sn-II) and Ph3PAuSR (Au-II) based on 2,6-di-tert-butyl-4-mercaptophenol (RSH) as radical scavengers and reducing agents were studied in model reactions. For Sn-II and Au-II the comparative study of cytotoxic action was made and the IC50 values on different cancer cell lines were found to be depended on the nature of metal. In general, Sn(IV) complexes possessed higher cytotoxicity than Au(I) complexes. In order to clarify the mechanism of cytotoxic mode of action the effect of compounds on Fe3+-induced lipid peroxidation, mitochondrial potential and mitochondrial permeability, cell cycle and induction of apoptosis was studied. Organotin compounds can bind tubulin SH-groups and inhibit its polymerization by a dose-dependent mechanism, whereas gold compounds inhibit Thioredoxin reductase (TrxR). In vivo experiments on acute toxicity of Sn-II and Au-II proved their moderate toxic action that opens prospects for the further study as antitumor agents.

Polymer-Drug Conjugate, a Potential Therapeutic to Combat Breast and Lung Cancer.

Cancer is a chronic disease that is responsible for the high death rate, globally. The administration of anticancer drugs is one crucial approach that is employed for the treatment of cancer, although its therapeutic status is not presently satisfactory. The anticancer drugs are limited pharmacologically, resulting from the serious side effects, which could be life-threatening. Polymer drug conjugates, nano-based drug delivery systems can be utilized to protect normal body tissues from the adverse side effects of anticancer drugs and also to overcome drug resistance. They transport therapeutic agents to the target cell/tissue. This review article is based on the therapeutic outcomes of polymer-drug conjugates against breast and lung cancer.

Renal clearable nanocarriers: Overcoming the physiological barriers for precise drug delivery and clearance

Physiological barriers encountered in the clinical translation of cancer nanomedicines inspire the community to more deeply understand nano-bio interactions in not only tumor microenvironment but also entire body and develop new nanocarriers to tackle these barriers. Renal clearable nanocarriers are one kind of these newly emerged drug delivery systems (DDSs), which enable drugs to rapidly penetrate into the tumor cores with no need of long blood retention and escape macrophage uptake in the meantime they can also enhance body elimination of non-targeted anticancer drugs. As a result, they can improve therapeutic efficacies and reduce side effects of anticancer drugs. Not limited to anticancer drugs, diagnostic agents can also be achieved with these renal clearable DDSs, which might also be applied to improve the precision in the gene editing and immunotherapy in the future.

Heat treatment and protective potentials of luteolin-7-O-glucoside against cisplatin genotoxic and cytotoxic effects

Cisplatin is an effective chemotherapeutic agent that has pronounced adverse effects. Using flavonoids is currently eliciting considerable interest. During extraction and conditioning, they usually undergo several physical treatments such as heat treatment, although it is not known whether thermal treatment might influence the pharmacological effects of flavonoids such as luteolin-7-O-glucoside (L7G). This study was undertaken to explore the protective role of native and heated L7G against DNA damage and oxidative stress induced by cisplatin. Balb/c mice were administered L7G before a single intraperitoneal injection of cisplatin (10mg/kg). Animals were sacrificed 24h after treatment with drugs. The geno-protective role of native and heated L7G was evaluated by comet assay. In addition to monitoring the activities of antioxidant enzymes, levels of malondialdehyde and reduced glutathione were assessed in the liver, kidney, brain, and spleen tissues. The results of the present study demonstrate that both heated and native L7G, at a dose of 40mg/kg b.w, were able to reduce the genotoxicity of cisplatin. They attenuate the oxidative stress (malondialdehyde, catalase, GPx, SOD, and GSH) and tissue damage (creatinine, IFNγ). Heat treatment did not alter the antigenotoxic effect observed for native L7G and showed similar effects to those of native L7G for all of the evaluated parameters. Our study reveals that L7G attenuates the side effects of anticancer drug and heat treatment did not alter his antigenotoxic and antioxidant the potential.

Patchouli alcohol attenuates 5-fluorouracil-induced intestinal mucositis via TLR2/MyD88/NF-kB pathway and regulation of microbiota

Intestinal mucositis causes great suffering to cancer patients who undergo chemotherapy and radiotherapy. Owing to the uncertain side effects of anticancer drugs to attenuate patients’ intestinal mucositis, many studies focused on traditional Chinese medicine (TCM). Patchouli alcohol (PA) is an active compound extracted from Pogostemon cablin, and has potent gastrointestinal protective effect. However, whether PA has an effect on intestinal mucositis is still unknown. Therefore, we established a rat model of intestinal mucositis via intraperitoneal injection of 5-fluorouracil, and intragastrically administrated PA (10, 20, and 40 mg/kg) to evaluate the effect of PA on intestinal mucositis. The routine observation (body weight, food intake, and diarrhea) in rats was used to detect whether PA had an effect on intestinal mucositis. Levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10, and MPO), mucosal barrier proteins (zonula occludens -1 (ZO-1), claudin-1, occludin, myosin light chain (MLC), and mucin-2) and intestinal microbiota were determined to elucidate the underlying mechanism of PA action on intestinal mucositis in rats. The results showed that PA could effectively improve body weight, food intake, and diarrhea in intestinal mucositis rats, preliminary confirming PA efficacy. Further experiments revealed that PA not only decreased the levels of TNF-α, IL-1β, IL-6, and MPO but also increased the level of IL-10 significantly. In addition, the expression of mucosal barrier proteins and microbiota community were also improved after PA treatment in diseased rats. Hence, PA may prevent the development and progression of intestinal mucositis by improving inflammation, protecting mucosal barrier, and regulating intestinal microbiota.

Advances in living cell-based anticancer therapeutics.

Nanomedicine has huge potential in cancer therapy due to its advantages of improving the solubility, increasing the bioavailability and reducing the side effects of anticancer drugs. However, the intratumoral accumulation of anticancer nanomedicine is still extremely low owing to multiple physiological barriers to drug delivery; thus, it is inefficient for cancer treatments. Inspired by the communication between natural cells and the body environment, living cell-based anticancer therapeutics have been developed as promising drug carriers or active drugs for cancer therapy. In this review, we will survey recent advances in living cell-based anticancer therapeutics by leveraging their physiological characteristics, from long circulating properties to tumor-homing capacity and anticancer immune responses. In addition, future prospects of this field will be discussed.

The Potential Role of the Peptide Amphiphiles in Targeted Drug Delivery to Tumors

Background: Targeted drug delivery approaches are intended to increase the effectiveness of drugs by carrying large doses of chemotherapeutic agents to the cancer cells and reduce negative side effects. Self-assembly of peptides can organize molecules into stable and well-defined nanostructures being very attractive for many biomedical applications including drug delivery. Objective: The objective of the current mini-review is to investigate the self-assembly behavior of peptide amphiphiles as nanocarriers under different biological factors in the tumor microenvironment. Method: Data from a range of resources like Google Scholar, PubMed, Medline, Scopus and Elsevier, and other valued journals have been reviewed carefully. Results: Structural changes of peptide amphiphiles in response to tumor microenvironment or tumor-specific enzymes are the promising trend, allowing the development of targeted therapy with high efficiency. However, significant improvement in cytotoxicity is achieved when peptide amphiphiles are designed in such a way to respond to multiple stimuli in tumor microenvironments. Conclusion: A multi- disciplinary research area may permit both to reduce the off-target side effects of anticancer drugs and achieve triggered drug delivery at disease sites.

One-pot synthesis of acid-degradable polyphosphazene prodrugs for efficient tumor chemotherapy.

In order to improve the therapeutic efficacy and reduce the side effects of anticancer drugs, stimuli-responsive and biodegradable drug-delivery systems have attracted significant attention in the past three decades. Herein, we report acid-responsive and degradable polyphosphazene nano-prodrugs synthesized via a one-pot cross-linking reaction of 4-hydroxybenzhydrazide-modified doxorubicin (BMD) with hexachlorocyclotriphosphazene (HCCP). The phenol groups in the as-synthesized BMD exhibited a high reactivity towards HCCP and in the presence of a basic catalyst the determined drug loading ratio of the nanoparticles, denoted as HCCP-BMD, was up to 85.64%. Interestingly, the hydrazone bonds in BMD and the skeleton of polyphosphazene tended to break down in acidic environments, and the antitumor active drug DOX was found to be released in an acidic tumor microenvironment (pH ∼ 6.8 for extracellular, and pH ∼ 5.0 for endosomes and lysosomes). The resulting HCCP-BMD prodrug exhibited high cytotoxicity to HeLa cells and could effectively suppress tumor growth, with negligible damage to normal tissues. We therefore believe that this acid- degradable polyphosphazene prodrug may offer great potential in various biomedical fields.

RETRACTED ARTICLE: Novel Therapeutic Approach Using Drug-loaded Adipose-derived Stem Cells for Pancreatic Cancer

We developed anticancer drug-conjugated biodegradable polymer-nanoparticle-loaded adipose-derived stem cells (AdSCs) as a tool for biodrug delivery systems for cancer therapy. Pirarubicin was conjugated in polylactic/glycolic acid (PLGA) followed by formation of nanoparticles (NPs), which were loaded with human AdSCs and cocultured. The pirarubicin-conjugated PLGA NP-loaded AdSCs (PirNP-AdSCs) were overall viable within 48 h and exhibited significantly enhanced migration activity. We confirmed that pirarubicin was gradually released into the culture medium from PirNP-AdSCs, and the conditioned medium significantly inhibited the proliferation activity and induced the apoptosis of human pancreatic cancer cells (KP1N). PirNP-AdSCs also significantly induced tumor cell apoptosis in an ex vivo culture system with KP1N-derived tumors, and there was increased invasion/migration of PirNP-AdSCs inside the tumor. Finally, we compared the therapeutic efficacy of the PirNP-AdSCs on KP1N-derived tumor growth with that of treatments of AdSCs alone, PirNPs alone or normal saline (control) in immunodeficient mice. Subcutaneous local administration of PirNP-AdSCs significantly inhibited tumor growth, inducing the apoptosis of tumor cells and vasculature compared with the other groups. The present therapeutic strategy might give rise to a novel cancer therapy minimizing the adverse side effects of anticancer drugs in patients who suffer from cancer.

Low side-effect and heat-shock protein-inhibited chemo-phototherapy nanoplatform via co-assembling strategy of biotin-tailored IR780 and quercetin

The side effects of anticancer drugs and tumor tolerance from heat shock protein expression are still a bottleneck for the current chemo-phototherapy. Although quercetin (Qu) is a naturally low-side effect anticancer drug and heat shock protein inhibitor for tailoring phototherapy, it is largely restricted by poor water solubility. Moreover, the near-infrared dye IR780-iodide (IR780), as a promising phototherapy agent, is also restricted from clinical applications due to its poor water solubility. Herein, we rationally designed a robust low side-effect and heat-shock protein-inhibited chemo-phototherapy nanoplatform via co-assembly of biotin-tailored IR780 (B780) and quercetin, defined as B780/Qu nanoparticles (B780/Qu NPs), which efficiently solved the poor water solubility of both IR780 and Qu. Moreover, the B780 endowed B780/Qu NPs with superior active tumor-targeted property and pH-responsive drug delivery. Thanks to the combination of chemo-phototherapy, the B780/Qu NPs with near infrared (NIR) laser irradiation exhibited excellent anti-tumor efficacy. Therefore, our B780/Qu NPs are very promising as an efficient low side-effect and heat-shock protein-inhibited chemo-phototherapy nanoplatform against tumors.

Effect of Primary and Secondary Beads of Carbon Enterosorbent on Haematological Parameters and Oxidative Stress Development Caused by Melphalan in Rats.

Background and Objectives: Side effects of anti-cancer drugs are usually accompanied by oxidative stress, including myelotoxicity. We evaluated the potential of oral highly activated micro-/macroporous carbon adsorbents (bulk density of 0.16 g/cm3, surface area calculation by Brunauer–Emmett–Teller model (SBET) > 2200 m2/g, derived from proprietary phenolic resin beads) to alleviate oxidative stress and myelotoxicity in rats. Materials and Methods: A single injection of cytostatic melphalan (L-PAM) at a dose of 4 mg/kg was used for modelling. Two forms of activated carbon were used: AC1—primary beads with the particle size range of 125–250 µm, and AC2—micronized AC1 with a mean particle size of ~1 µm. We measured haematological parameters white blood cells, red blood cells, platelet count, and haemoglobin level. Oxidative stress intensity was evaluated using the following markers: total levels of reactive oxygen species (ROS) in blood plasma; catalase activity (CAT) and pro-oxidant/antioxidant ratio in blood haemolysate samples; level of reduced glutathione (GSH) in liver tissues; oxidative modification of proteins, OPM (APHD, aldehyde–dinitrophenylhydrazone derivatives and KPHD, ketone dinitrophenylhydrazone derivatives) and malonic dialdehyde (MDA) in blood plasma and liver samples. Results: AC2 administration promoted significant myeloprotective effect: 1.5-fold increase in leukocytes, 2-fold in neutrophils, 1.5-fold in lymphocytes, and 1.23-fold in platelet count compared to the experimental Melphalan Group. At the same time, AC1 administration resulted in a slight increase in haematological parameters. Both ACs positively corrected important, but diverse, components of oxidative stress. They significantly reduced oxidative modification of blood and liver proteins (especially the AC1 form), normalized the level of reduced glutathione, pro-oxidant/antioxidant ratio and other markers. For some markers, such as ROS production in blood plasma, the use of enterosorbents resulted in non-significant a shift towards normal parameters. Conclusions: Oral activated carbon adsorbents reduce oxidative stress intensity and myelotoxicity; they can be promising means to combat the adverse effects of chemotherapy in clinical practice.

Anti-Diarrheal Drug Repositioning in Tumour Cell Cytotoxicity.

Drug repositioning is becoming an ideal strategy to select new anticancer drugs. In particular, drugs treating the side effects of chemotherapy are the best candidates. In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs (nifuroxazide and rifaximin). Anti-proliferative effect against breast cancer cells (MDA-MB-231, MCF-7 and T47D) was assessed by MTT analysis, the Brdu incorporation, mitochondrial permeability and caspase-3 activity. Both the drugs displayed cytotoxic effects on MCF-7, T47D and MDA-MB-231 cells. The lowest IC50 values were obtained on MCF-7 cells after 24, 48 and 72 hours of treatment while T47D and MDA-MB-231 were more resistant. The IC50 values on T47D and MDA-MB-231 cells became significantly low after 72 hours of treatment showing a late cytotoxicity effect especially of nifuroxazide but still less important than that of MCF-7 cells. According to the IC50 values, the non-tumour cell line HEK293 seems to be less sensitive to cytotoxicity especially against rifaximin. Both the drugs have shown an accumulation of rhodamine 123 as a function of the rise of their concentrations while the Brdu incorporation decreased. Despite the absence of a significant difference in the cell cycle between the treated and non-treated MCF-7 cells, the caspase-3 activity increased with the drug concentrations rise suggesting an apoptotic effect. Nifuroxazide and rifaximin are used to overcome the diarrheal side effect of anticancer drugs. However, they have shown to be anti-tumour drugs which make them potential dual effective drugs against cancer and the side effects of chemotherapy.

The Apoptotic Pathway Induced by Vincristine in Mouse Proliferating and Resting Normal Lymphocytes and Lymphoma Cell Line

Background: Most anti-cancer drugs target mitosis and induce apoptosis in cancerous cells. In the immune system, proliferation and apoptosis of lymphocytes are indeed essential modulating elements. Objectives: In this study, we have investigated the effect of vincristine on normal resting and normal proliferating lymphocytes comparing with cancerous cells. Methods: Resting and proliferating splenocytes from mice and BCL1 (mouse lymphoma cell line) were cultured with different concentrations of vincristine for 48 hours, and cell lysates were prepared. The activity of caspases 3, 8, and 9 in cell lysates was measured using specific chromogenic substrates DEVD-pNA for caspase 3, IETD-pNA for caspase 8, and LEHD-pNA for caspase 9, the activity calculated as µmol/min/mg protein. Results: In the BCL1 cell line, the activity of both caspases 8 and 9 and caspase 3 increased at the presence of vincristine (5 µg/mL). In resting splenocytes, however, only a mild increase in caspase 9 activity was observed without any change in the activity of caspases 8 or 3. In the same situation, the activity of caspase 3 and 9 (but not caspase 8) elevated in proliferating cells exposed to vincristine. Nearly similar results were obtained with higher concentrations of vincristine (up 20 µg/mL). Conclusions: The results suggesting that vincristine may induce internal pathways of apoptosis in normal and cancerous cells while extrinsic pathway was induced in cancerous cells. On the other hand, the effects are highly dependent on the activation status of normal cells, and affirms that responding immune cells should be more seriously noticed when side effects of anticancer drugs are estimated.

Tumor-Specific Expansion of Oxidative Stress by Glutathione Depletion and Use of a Fenton Nanoagent for Enhanced Chemodynamic Therapy.

Amplifying intracellular oxidative stress effectively destroys cancer cells. In addition, iron-mediated Fenton reaction converts endogenous H2O2 to produce hypertoxic hydroxyl radical (•OH), resulting in irreversible oxidative damage to combat tumor cells. This method is known as chemodynamic therapy (CDT). Overexpressed glutathione (GSH) in tumor cells efficiently scavenges •OH, significantly reducing the curative effects of CDT. To overcome this challenge and enhance intracellular oxidative stress, iron oxide nanocarriers loaded with β-lapachone (Lapa) drugs (Fe3O4-HSA@Lapa) were constructed and had both Fenton-like agents and GSH depletion properties to amplify intracellular oxidative stress. Release of Lapa selectively increases tumor site-specific generation of H2O2 via NAD(P)H: quinone oxidoreductase 1 (NQO1) catalysis. Subsequently, the iron ions released from the ionization of Fe3O4 in the acidic environment selectively convert H2O2 into highly toxic •OH by Fenton reaction, dramatically improving CDT with minimal systemic toxicity due to low NQO1 expression in normal tissues. Meanwhile, released Lapa consumes GSH in the tumor, amplifying oxidative stress and enhancing the efficacy of CDT. Designed Fe3O4-HSA@Lapa nanoparticles (NPs) exhibit perfect targeting capability, prolonged blood circulation, and increased tumor accumulation. Furthermore, Fe3O4-HSA@Lapa NPs effectively enhance the inhibition of tumor growth and reduce the side effects of anticancer drugs. This work establishes a remarkably enhanced tumor-selective CDT against NQO1-overexpressing tumors by significantly inducing intratumoral oxidative stress with minimal side effects.

Self-assembled green tea polyphenol-based coordination nanomaterials to improve chemotherapy efficacy by inhibition of carbonyl reductase 1

Nanomedicine has become a promising approach to improve cancer chemotherapy. It remains a major challenge how to enhance anti-drug efficacy and reduce side effects of anti-cancer drugs. Herein, we report a self-assembled nanoplatform (FDEP NPs) by integration of doxorubicin (DOX) and epigallocatechin-3-O-gallate (EGCG) with the help of coordination between Fe3+ ions and polyphenols. The EGCG from FDEP NPs could inhibit the expression of carbonyl reductase 1 (CBR1) protein and thereby inhibit the doxorubicinol (DOXOL) generation from DOX both in vitro and in vivo, thus the efficacy of DOX to cancerous cells is improved significantly. More importantly, the FDEP NPs could reduce cardiac toxicity and the DOX mediated toxicity to blood cells due to the repression of DOXOL production. Moreover, the blood half-life of FDEP NPs is longer than 23 h as determined by positron emission tomography (PET) imaging of biodistribution of radiolabelled NPs and HPLC measurement of plasma level of DOX, ensuring high tumor accumulation of FDEP NPs by enhanced permeability and retention (EPR) effect. The FDEP NPs also exhibited much improved antitumor effect over free drugs. Our work sheds new light on the engineering of nanomaterials for combination chemotherapy and may find unique clinical applications in the near future.

PH-Triggered Charge-Reversal Mesoporous Silica Nanoparticles Stabilized by Chitosan Oligosaccharide/Carboxymethyl Chitosan Hybrids for Effective Intracellular Delivery of Doxorubicin.

Surface modification of mesoporous silica nanoparticles (MSNs) is a promising way to enhance therapeutic efficacy and minimize side effects of anticancer drugs. In this work, MSNs with reduced particle size and optimum pore diameter were obtained and catalyzed by ammonia/triethanolamine. In view of the negatively charged carboxymethyl chitosan (CMC) and positively charged chitosan oligosaccharide (CS), the pH-triggered charge-reversal CS/CMC bilayer was designed as a stimuli-responsive switch for MSNs via the protonation and deprotonation effect. The results showed that MSNs-CS/CMC were core-shell and mesoporous in structure. Surface charge conversion and pH dependence were clearly observed in the doxorubicin hydrochloride (DOX) delivery. The intracellular uptake indicated that DOX@MSNs-CS/CMC could be distributed in the cytoplasm of MCF-7 cells and exhibited lower toxicity, which would improve the stability and prolong the retention time compared to free DOX and unmodified DOX@MSNs at pH 7.4. Moreover, the cellular uptake and internalization of DOX@MSNs-CS/CMC were enhanced to promote drug delivery into the cell nucleus at pH 6.5. The biocompatible and surface-charge-reversible MSNs-CS/CMC have the potential to prolong the retention time in the bloodstream, facilitate the endosome escape, and enrich the targeted antitumor strategy, providing an alternative platform for efficient drug delivery in breast cancer therapy.

Research progress in stimuli-responsive mesoporous silica nano drug delivery systems for tumor therapy

In recent years, mesoporous silica nanoparticles (MSNs) have been widely used in the construction of various intelligent drug delivery systems due to their unique and excellent properties. The stimuli-responsive drug delivery system based on mesoporous silica nanoparticles can effectively load anticancer drugs and target them to tumor cells, and then responsively release anticancer drugs under the action of specific stimulation signals. The method of specifically delivering anticancer drugs to target sites not only can greatly improvethe drug efficacy, but also effectively reduce the side effects of anticancer drugs on normal tissues and organs. Thereby the advantages of anticancer drugs in tumor therapy are improved. In this paper, the applications and developments of stimuli-responsive mesoporous silica nano drug delivery systems in tumor therapy were summarized. Key words: Mesoporous silica nanoparticles; Stimuli-responsive; Controlled release; Tumor therapy

Sequential activation of anticancer therapy triggered by tumor microenvironment-selective imaging

The combination of imaging and anticancer therapy has recently emerged as a promising strategy. However, nonspecific imaging signals and distribution of anticancer drugs at normal tissues limit the specificity of the combination therapy. To overcome the challenges, we designed a system which can selectively visualize cancer tissues and initiate the subsequent action of therapeutic molecules in tumor microenvironment. Exploiting the overexpression of matrix metalloproteinase (MMP) in the tumor microenvironment, we designed a graphene oxide (GO)-based nanosheet system loaded with a pegylated MMP-cleavable imaging probe and an anticancer peptide shielded under the imaging probe. GO loaded with pegylated imaging probe derivative and anticancer buforin IIb peptide (IPGO/BF) was not fluorescent and BF hidden within pegylated surfaces did not exert anticancer activity. However, in tumor microenvironment, IPGO/BF selectively provided imaging by liberating pegylated fluorescent moiety. The cleavage of MMP-sensitive peptide triggered imaging signal and subsequent exposure of shielded BF on GO and enhanced its therapeutic function. SCC7 tumor-bearing mice treated with IPGO/BF exhibited selective fluorescence in tumor tissues, and greater imaging signal-dependent antitumor effects compared with other groups. The selective imaging-dependent sequential activation of anticancer therapy in tumor microenvironment would be a feasible strategy to reduce the nonspecific false-positive signals of tumor imaging and undesirable side effects of anticancer drugs at normal tissues.

Design, Synthesis, and Biological Evaluation of a Conjugate of 5-Fluorouracil and an LSD1 Inhibitor

Prodrug approaches are useful for enhancing the efficacies and reducing the side effects of anticancer drugs. Previously, we proposed a prodrug strategy for targeting cancers overexpressing lysine-specific demethylase 1 (LSD1), namely, conjugates of trans-2-phenylcyclopropylamine (PCPA, an LSD1 inhibitor) and anticancer drugs. In this study, we applied this prodrug strategy to the anticancer agent 5-fluorouracil (5-FU). In vitro assays showed that the PCPA-5-FU conjugate (1) released 5-FU upon the inhibition of LSD1. Furthermore, the conjugate (1) exerted an antiproliferative effect on colon cancer HCT116 cells. Thus, the PCPA-5-FU conjugate (1) was able to function as a prodrug of 5-FU, activated by LSD1 inhibition, and provided a useful new lead structure for further development.

Apoferritin nanocages with Au nanoshell coating as drug carrier for multistimuli-responsive drug release

Cancer is one of the major causes of mortality worldwide. Therefore, it is necessary to provide an effective method of tumor therapy. Herein, we designed a new type of composite particle, apoferritin (APO) encapsulated doxorubicin (DOX), and the surface of APO was modified with Au nanoshell. As a nanocarrier, APO can carry chemotherapy drug DOX (APODOX) and release drug under acidic and high temperature conditions to reduce side effects of anticancer drugs. After covering Au nanoshell (APODOX-Au), the photothermal effect can be produced because of the unique surface plasmon resonance properties of gold nanoshell. This nanoplatform also provides the multi-stimuli responsive drug release system, which can achieve drug release in different conditions and have great potential in biomedical applications. Our investigation has demonstrated that APODOX-Au has good stability, high dispersibility and biocompatibility in vitro. The strong near-infrared absorption and good photothermal effect make sure the quick response to environmental changes (pH, temperature) to achieve drug release. These findings indicate that these nanoparticles have a potential application value in cancer treatment.