Delivery Of Doxorubicin Research Articles

Comparing organic and metallo-organic hydrazone molecular cages as potential carriers for doxorubicin delivery.

Molecular cages are three-dimensional supramolecular structures that completely wrap guest molecules by encapsulation. We describe a rare comparative study between a metallo-organic cage and a fully organic analogous system, obtained by hydrazone bond formation self-assembly. Both cages are able to encapsulate the anticancer drug doxorubicin, with the organic cage forming a 1 : 1 inclusion complex with μM affinity, whereas the metallo-organic host experiences disassembly by interaction with the drug. Stability experiments reveal that the ligands of the metallo-organic cage are displaced in buffer at neutral, acidic, and basic pH, while the organic cage only disassembles under acidic conditions. Notably, the organic cage also shows minimal cell toxicity, even at high doses, whilst the doxorubicin-cage complex shows in vitro anti-cancer activity. Collectively, these results show that the attributes of the pure organic molecular cage are suitable for the future challenges of in vivo drug delivery using molecular cages.

Doxorubicin delivery systems based on polypeptide nanoparticles for subcutaneous administration in cancer therapy

Polypeptide-based doxorubicin delivery systems were prepared and their physicochemical and functional properties, such as size, encapsulation efficiency, stability, release of doxorubicin in various media and cytotoxicity, were characterized. An in vivo study revealed an effective reduction of tumor growth when these systems were administered subcutaneously.

Targeted delivery of doxorubicin by SP5-52 peptide conjugated exosome nanoparticles into lung tumor: An in vitro and in vivo study

Here, SP5-52 peptide conjugated exosome nanostructures were developed for targeted delivery of Doxorubicin (DOX) into lung tumor. Exosomes extracted from the serum of Balb/c mice, were characterized in terms of structure and physicochemical properties. Based on the results, the size and zeta potential of exosome NPs were 67 nm and −5 mV, respectively, which was slightly increased after SP5-52 conjugation and DOX loading. The in vitro cell studies displayed that targeted DOX-loaded exosomes had higher cytotoxicity, cellular uptake, and accumulation in LL/2 cell lines compared with non-targeted DOX-loaded exosomes and control groups. Moreover, the therapeutic efficacy of the prepared formulations was evaluated in lung tumor bearing Balb/c mice within 21 days. Accordingly, targeted DOX-loaded exosomes had effectively treated the lung tumor in comparison to other groups. The rate of survival in the mice treated with targeted exosomes was also 35 % higher than other groups; while, the mortality rate was lower. The histopathological evaluation confirmed the accepted off-targeted properties of the targeted exosomes as lower toxicity was observed in different organs rather than lung. This study presents an effective anticancer drug delivery system for specific targeting of induced lung tumor, which could be useful in the treatment of malignant lung cancers in the future.

Chemosensitization of tumors via simultaneous delivery of STAT3 inhibitor and doxorubicin through HPMA copolymer-based nanotherapeutics with pH-sensitive activation

We synthesized three novel STAT3 inhibitors (S3iD1-S3iD3) possessing oxoheptanoic residue enabling linkage to HPMA copolymer carrier via a pH-sensitive hydrazone bond. HPMA copolymer conjugates bearing doxorubicin (Dox) and our STAT3 inhibitors were synthesized to evaluate the anticancer effect of Dox and STAT3 inhibitor co-delivery into tumors. S3iD1–3 and their copolymer-bound counterparts (P-S3iD1-P-S3iD3) showed considerable in vitro cytostatic activities in five mouse and human cancer cell lines with IC50 ~0.6–7.9 μM and 0.7–10.9 μM, respectively. S3iD2 and S3iD3 were confirmed to inhibit the STAT3 signaling pathway. The combination of HPMA copolymer-bound Dox (P-Dox) and P-S3iD3 at the dosage showing negligible toxicity demonstrated significant antitumor activity in B16F10 melanoma-bearing mice and completely cured 2 out of 15 mice. P-Dox alone had a significantly lower therapeutic activity with no completely cured mice. Thus, polymer conjugates bearing STAT3 inhibitors may be used for the chemosensitization of chemorefractory tumors.

A Mesoporous Magnetic Fe3O4/BioMOF-13 with a Core/Shell Nanostructure for Targeted Delivery of Doxorubicin to Breast Cancer Cells.

In the current project, magnetic Bio-MOF-13 was used as an efficient carrier for the targeted delivery and controlled release of doxorubicin (DOX) to MDA-MB-231 cells. Magnetic Bio-MOF-13 was prepared by two strategies and compared to determine the optimal state of the structure. In the first path, Bio-MOF-13 was grown in situ on the surface of Fe3O4 nanoparticles (core/shell structure), while in the second method, the two presynthesized materials were mixed together (surface composite). Core/shell structure, among prepared nanocomposites, was chosen for biological evaluation due to its favorable structural features like a high accessible surface area and pore volume. Also, it is highly advantageous for drug release due to its ability to selectively release DOX in the acidic pH of breast cancer cells, while preventing any premature release in the neutral pH of the blood. Drug release from the carrier structure is precisely controlled not only by pH but also by an external magnetic field, guaranteeing accurate drug delivery at the intended location. Confocal microscopy and flow cytometry assay clearly confirms the increase in drug concentration in the MDA-MB-231 cell line after external magnet applying. This point, along with the low toxicity of the carrier components, makes it a suitable candidate for injectable medicine. According to MTT results, the percentage of viable MDA-MB-231 cells after treatment with 10 μL of DOX@Fe3O4/Bio-MOF-13 core/shell composite in different concentrations, in the presence and absence of magnetic field is 0.87 ± 0.25 and 2.07 ± 0.15, respectively. As a result, the DOX@Fe3O4/Bio-MOF-13 core/shell composite was performed and approved for targeted drug delivery and magnetic field-assisted controlled release of DOX to the MDA-MB-231 cell line.

Bioengineered DNA-decorated UiO-66-based nanocarriers for combined administration of doxorubicin and sorafenib: Hepatocellular carcinoma treatment and chemotherapy

Natural biomaterials were used to decorate UiO-66-NH2 to develop a platform for co-drug delivery of doxorubicin and sorafenib as a cost-effective and easy way to use a drug delivery system (DDS). To properly characterize the modified MOFs, standard analytical methods were used. Then doxorubicin and sorafenib were loaded into and onto the porosity of the MOF, UiO-66-NH2. The surface morphological analysis, FESEM, and TEM images revealed the hexagonal structure of the UiO-66-NH2, demonstrating the successful synthesis of these green MOFs. Internalization and loading of doxorubicin on the MCF-7 cell line was investigated with two-dimensional fluorescence microscopy, which shows that drug internalizations on the cancerous cells were successful and promising. The drug payload of 49.5% and 31.2% for doxorubicin and sorafenib were attained, respectively. Study on the MCF-7 HT-29 and HEK-293 cell lines exhibited excellent cell viability when subjected to both low and high concentrations of 0.1 µg.mL−1 and 50 µg.mL−1, respectively. After 24 h of treatment, the relative cell viability of 85.1%, 88.1%, and 76.8% was achieved for the HT-29, HEK-293, and MCF-7 cell lines, respectively. In addition, after 48 h of treatment, the relative cell viability of 82.5%, 83.5%, and 68.5% was recorded, respectively. However, the percentage of cell viability was dramatically reduced by coating the nanocarrier with Ginkgo biloba leaf extract and E. Coli DNA (62.6%, 40.9%, and 45.1% for 24 h treatment and 62.1%, 38.5%, and 38.9% for 48 h treatment in HEK-293, HT-29, and MCF-7 cell lines, respectively).

Biopolymer‐based nanoparticles as promising candidate for inducing apoptosis in liver cancer cells

AbstractLiver cancer is one of the most common causes of death all around the globe. On the other hand, conventional modalities, such as chemotherapy and surgery, have not been effectively suppressed cancer incidence due to some deficiencies. As a result, a novel folic acid (FA)‐decorated poly lactic‐co‐glycolic acid (PLGA)‐Alginate (Alg) nanocarrier was efficiently developed for active doxorubicin (Dox) delivery to human HepG2 liver cancer cells. The in vitro assays, including cell viability assay (MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) test), apoptosis, cell cycle arrest, and cellular uptake, were applied to evaluate the cancer cell growth suppression and apoptosis‐inducing ability of the nanocarrier. More than 85% cytotoxicity was attained after 24 h of treatment with 400‐nM concentration of FA‐PLGA‐Dox‐Alg. More than 21% and 61% apoptosis were observed after 24 h of treatment with 100‐nM concentrations of FA‐PLGA‐Dox‐Alg in apoptosis and cell cycle arrest assays. The cellular uptake of the FA‐PLGA‐Alg nanocarrier was about 30% higher than that of the PLGA‐Alg carrier which indicated the cancer cell targeting ability of the FA‐PLGA‐Alg sample. These results have indicated the potential capability of FA‐PLGA‐Dox‐Alg in the inhibition of liver cancer cells.

Aptamer-Modified Tetrahedral DNA Nanostructures as Drug Delivery System for Cancer Targeted Therapy.

Improving the selective delivery and uptake efficiency of chemotherapeutic drugs remains a challenge for cancer-targeted therapy. In this work, a DNA tetrahedron is constructed as a targeted drug delivery system for efficient delivery of doxorubicin (Dox) into cancer cells. The DNA tetrahedron is composed of a tetrahedral DNA nanostructure (TDN) with two strands of AS1411 aptamer as recognition elements which can target the nucleolin protein on the cell membrane of cancer cells. The prepared DNA tetrahedron has a high drug-loading capacity and demonstrates pH-responsive Dox release properties. This enables efficient delivery of Dox into targeted cancer cells while reducing side effects on nontarget cells. The proposed drug delivery system exhibits significant therapeutic efficacy in vitro compared to free Dox. Accordingly, this work provides a good paradigm for developing a targeted drug delivery system for cancer therapy based on DNA tetrahedrons.

Optimized DOX Drug Deliveries via Chitosan-Mediated Nanoparticles and Stimuli Responses in Cancer Chemotherapy: A Review.

Chitosan nanoparticles (NPs) serve as useful multidrug delivery carriers in cancer chemotherapy. Chitosan has considerable potential in drug delivery systems (DDSs) for targeting tumor cells. Doxorubicin (DOX) has limited application due to its resistance and lack of specificity. Chitosan NPs have been used for DOX delivery because of their biocompatibility, biodegradability, drug encapsulation efficiency, and target specificity. In this review, various types of chitosan derivatives are discussed in DDSs to enhance the effectiveness of cancer treatments. Modified chitosan-DOX NP drug deliveries with other compounds also increase the penetration and efficiency of DOX against tumor cells. We also highlight the endogenous stimuli (pH, redox, enzyme) and exogenous stimuli (light, magnetic, ultrasound), and their positive effect on DOX drug delivery via chitosan NPs. Our study sheds light on the importance of chitosan NPs for DOX drug delivery in cancer treatment and may inspire the development of more effective approaches for cancer chemotherapy.

Fabrication and characterization of doxorubicin conjugated bimetallic gold and platinum nanoparticles for human cancer cells and its cell death mechanism

An environmentally friendly preparation technique was used to explore the mechanism of action of hybrid hydrophilic bimetallic gold-platinum (Au@Pt-NPs) against human cancer cell lines, followed by conjugation with doxorubicin (DOX). The synthesized DOX-loaded Au@Pt-NPs (DOX/Au@Pt-NPs) were examined using transmission electron microscopy, X-ray diffraction, and UV–vis spectroscopy to determine their physicochemical characteristics. Using a straightforward incubation method, phytochemicals-mediated capping efficiency and loading of DOX onto the Au@Pt-NPs surface (84%) was demonstrated by FT-IR spectroscopy. Studies on the release kinetics of DOX under acidic tumor conditions revealed a pH-regulated dependence response. According to the in vitro anticancer assessment, human cancer cells treated with DOX-loaded Au@Pt-NPs demonstrated a 3-fold increase in apoptosis compared to DOX treatment alone. Additionally, the DOX/Au@Pt-NPs nanocarrier demonstrated a time-dependent increase in phosphatidylserine flipping, an apoptosis induction marker, and a cell-specific reaction in HeLa and HepG2 cells, according to luminescent results from a real-time, bioluminescent recombinant annexin V test. According to the results, the manufacturing process is simple, and the hydrophilic Au@Pt-NPs were successful in DOX delivery and loading against human cancer cell lines, indicating their prospective as a supplementary for cervical and hepatocellular cancer therapy.

PH/redox responsive size‐switchable intelligent nanovehicle for tumor microenvironment targeted DOX release

Tumor microenvironment (TME) targeted strategy could control the drug release in tumor cells more accurately and creates a new opportunity for enhanced site-specific targeted delivery. In this study, (PAA-b-PCL-S-S-PCL-b-PAA) copolymeric nanoparticles (NPs) with size-switchable ability and dual pH/redox-triggered drug release behavior were designed to significantly promote cancer uptake (cell internalization of around 100% at 30 min) and site-specific targeted doxorubicin (DOX) delivery in MDA-MB-231 tumor cells. NPs surface charge was shifted from − 17.8 to − 2.4 and their size shrunk from 170.3 to 93 nm in TME. The cell cycle results showed that DOX-loaded NPs showed G2/M (68%) arrest, while free DOX showed sub-G1 arrest (22%). Apoptosis tests confirmed that the cells treated with DOX-loaded NPs showed a higher amount of apoptosis (71.6%) than the free DOX (49.8%). Western blot and RT-PCR assays revealed that the apoptotic genes and protein levels were significantly upregulated using the DOX-loaded NPs vs. the free DOX (Pvalue < 0.001). In conclusion, dual pH/redox-responsive and size-switchable DOX-loaded NPs developed here showed outstanding anti-tumoral features compared with free DOX that might present a prospective platform for tumor site-specific accumulation and drug release that suggest further in vivo research.

Hydroxyapatite Nanocrystals Integrated into Mesoporous Silica for Sustained Delivery of Doxorubicin

Hydroxyapatite Nanocrystals Integrated into Mesoporous Silica for Sustained Delivery of Doxorubicin

Antibody-decorated chitosan-iodoacetamide-coated nanocarriers for the potential delivery of doxorubicin to breast cancer cells

Using an active targeting approach of chemotherapeutics-loaded nanocarriers (NCs) with monoclonal antibodies is a potential strategy to improve the specificity of the delivery systems and reduce adverse reactions of chemotherapeutic drugs. Specific targeting of the human epidermal growth factor receptor-2 (HER-2), expressed excessively in HER-2-positive breast cancer cells, can be achieved by conjugating NCs with an anti–HER-2 monoclonal antibody. We constructed trastuzumab-conjugated chitosan iodoacetamide-coated NCs containing doxorubicin (Tras-Dox-CHI-IA-NCs) as a tumor-targeted drug delivery system, during the study. Chitosan-iodoacetamide (CHI-IA) was synthesized and utilized to prepare trastuzumab-conjugated NCs (Tras-NCs). The morphology, physicochemical properties, drug loading, drug release, and biological activities of the NCs were elucidated. The Tras-NCs were spherical, with a particle size of approximately 76 nm, and had a positive zeta potential; after incorporating the drug, the size of the Tras-NC increased. A prolonged, 24-h drug release from the NCs was achieved. The Tras-NCs exhibited high cellular accumulation and significantly higher antitumor activity against HER-2-positive breast cancer cells than the unconjugated NCs and the drug solution. Therefore, Tras-Dox-CHI-IA-NCs could be a promising nanocarrier for HER-2-positive breast cancer.

Doxorubicin bioavailability to human hemoglobin and cancer cells via MOF-A520

Cancer is one of the most serious and challenging issues in the life sciences, with complicated and multifactorial mechanisms making it difficult to manage. With this complexity comes various strategies for attacking tumors, including using nanomaterials to target tumor cells, bioavailability and deliver anticancer drugs directly. Doxorubicin (DOX) is a well-known and powerful anticancer drug, but its high toxicity limits its application. Intending to reduce the cytotoxic effects of DOX on normal cell line and deliver it to cancerous cell line, the present study attempts to design and synthesize a modified metal–organic framework (MOF) named A520 and a composite containing DOX (A520@DOX). The synthesized MOFs were characterized using X-ray diffraction (XRD), electron microscopy (TEM and FESEM), and FTIR. Subsequently, the toxicity of DOX was assessed at the cellular and molecular levels using MTT assays (for the cell lines MCF −10A and MCF-7) and various biophysical assays targeting human hemoglobin (Hb). Following expectations, free DOX was highly cytotoxic and strongly affected Hb structure (converting it into methemoglobin species), while the toxicity was significantly reduced in the A520@DOX composite form. It is important to mention that DOX released from the A520@DOX was significantly pH-sensitive, so it was more pronounced in acidic pH 5 (resembling a cancerous pH environment). Furthermore, the effect of DOX released from A520@DOX resulted in more oxyHb and deoxyHb species as functional Hb species. The present study used an effective DOX delivery and bioavailability nanosystem to control cytotoxicity and ensure slow drug release.

MiRNAs as short non-coding RNAs in regulating doxorubicin resistance.

The treatment of cancer patients has been prohibited by chemoresistance. Doxorubicin (DOX) is an anti-tumor compound disrupting proliferation and triggering cell cycle arrest via inhibiting activity of topoisomerase I and II. miRNAs are endogenous RNAs localized in cytoplasm to reduce gene level. Abnormal expression of miRNAs changes DOX cytotoxicity. Overexpression of tumor-promoting miRNAs induces DOX resistance, while tumor-suppressor miRNAs inhibit DOX resistance. The miRNA-mediated regulation of cell death and hallmarks of cancer can affect response to DOX chemotherapy in tumor cells. The transporters such as P-glycoprotein are regulated by miRNAs in DOX chemotherapy. Upstream mediators including lncRNAs and circRNAs target miRNAs in affecting capacity of DOX. The response to DOX chemotherapy can be facilitated after administration of agents that are mostly phytochemicals including curcumol, honokiol and ursolic acid. These agents can regulate miRNA expression increasing DOX's cytotoxicity. Since delivery of DOX alone or in combination with other drugs and genes can cause synergistic impact, the nanoparticles have been introduced for drug sensitivity. The non-coding RNAs determine the response of tumor cells to doxorubicin chemotherapy. microRNAs play a key role in this case and they can be sponged by lncRNAs and circRNAs, showing interaction among non-coding RNAs in the regulation of doxorubicin sensitivity.

α-Tocopherol Polyethylene Glycol 1000 Succinate-Based Cationic Liposome for the Intracellular Delivery of Doxorubicin in MDA-MB-231 Triple-Negative Breast Cancer Cell Line.

Present research work reports the development of doxorubicin (DOX) loaded α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes. The developed formulation was evaluated for its anticancer potential and intracellular uptake against the MDA-MB-231 breast cancer cell line. Moreover, hemocompatibility studies were also done on human blood red blood cells for the determination of blood compatibility. The prepared doxorubicin-loaded TPGS liposomes (DOX-LIPO-TPGS) and doxorubicin-loaded cationic liposomes (DOX-LIPO+-TPGS) reveal vesicle size (177.5 ± 2.5 and 201.7 ± 2.3 nm), polydispersity index (0.189 ± 0.01 and 0.218 ± 0.02), zeta potential (-36.9 ± 0.7 and 42 ± 0.9 mv), and % entrapment efficiency (65.88% ± 3.7% and 74.5% ± 3.9%). Furthermore, in vitro, drug release kinetics of the drug alone and drug from formulation shows sustained release behavior of developed formulation with 99.98% in 12 h and 80.98% release of the drug in 72 h, respectively. In addition, cytotoxicity studies and cellular DOX uptake on the MDA-MB-231 breast cancer cell line depict higher cytotoxic and drug uptake potential with better hemocompatibility of DOX-LIPO+-TPGS with respect to DOX. The data from the study revealed that TPGS plays an important role in enhancing the formulation's quality attributes like stability, drug release, cytotoxicity, and hemocompatibility behavior. This may serve that TPGS-coated cationic liposome as a vital candidate for the treatment of cancer and drug delivery in case of breast cancer.

Targeted Hyperbranched Nanoparticles for Delivery of Doxorubicin in Breast Cancer Brain Metastasis.

Breast cancer brain metastases (BM) are associated with a dismal prognosis and very limited treatment options. Standard chemotherapy is challenging in BM patients because the high dosage required for an effective outcome causes unacceptable systemic toxicities, a consequence of poor brain penetration, and a short physiological half-life. Nanomedicines have the potential to circumvent off-target toxicities and factors limiting the efficacy of conventional chemotherapy. The HER3 receptor is commonly expressed in breast cancer BM. Here, we investigate the use of hyperbranched polymers (HBP) functionalized with a HER3 bispecific-antibody fragment for cancer cell-specific targeting and pH-responsive release of doxorubicin (DOX) to selectively deliver and treat BM. We demonstrated that DOX-release from the HBP carrier was controlled, gradual, and greater in endosomal acidic conditions (pH 5.5) relative to physiologic pH (pH 7.4). We showed that the HER3-targeted HBP with DOX payload was HER3-specific and induced cytotoxicity in BT474 breast cancer cells (IC50: 17.6 μg/mL). Therapeutic testing in a BM mouse model showed that HER3-targeted HBP with DOX payload impacted tumor proliferation, reduced tumor size, and prolonged overall survival. HER3-targeted HBP level detected in ex vivo brain samples was 14-fold more than untargeted-HBP. The HBP treatments were well tolerated, with less cardiac and oocyte toxicity compared to free DOX. Taken together, our HER3-targeted HBP nanomedicine has the potential to deliver chemotherapy to BM while reducing chemotherapy-associated toxicities.

DDEL-09. SATURATED FATTY ACID EMULSION OPENS THE BLOOD-BRAIN BARRIERS AND ENHANCES DRUG DELIVERY

Abstract PURPOSE To evaluate whether saturated fatty acid (SFA) emulsion affects the BBB and whether drug delivery is promoted with the aid of SFA in the brain. MATERIAL AND METHODS Each SFA (butyric, valeric, caproic, enantic and caprylic acid) emulsion was infused into the right common carotid artery in a rat model. Trypan blue staining for qualitative and semiquantitative analysis of the BBB opening was performed. A transmission electron microscopic (TEM) exam with the contrast media for morphologic evaluation of the tight junction was obtained. Delivery of doxorubicin in the brain was determined by fluorometric analysis. Delivery of temozolomide (TMZ) through the BBB was studied by desorption electrospray ionization (DESI)-MS imaging. RESULTS The ipsilateral hemisphere revealed positive trypan blue staining in all five SFA emulsion groups. Ratios of the ipsilateral to the contralateral hemisphere of in trypan blue permeability with hue analysis was above 1.0. As the carbon number in the used SFA increased, the ratio of trypan blue permeability increased and was statistically significant (P &amp;lt; 0.05). The tight junction and neural interstitium were filled with the contrast media in all five SFA emulsion groups. Delivery of doxorubicin (P &amp;lt; 0.05) and TMZ were significantly high in the ipsilateral hemisphere compared to the contralateral hemisphere. In the caprylic acid group, the BBB opening and drug delivery were highest among the five SFA groups. CONCLUSION SFA emulsion with intraarterial infusion opened the BBB and drug delivery was enhanced consequently. Thus, SFA emulsion might be another strategy for the research of BBB opening and promotion of drug delivery in the brain.

Folic acid-decorated vitamin E Poly(ethylene glycol) monoplatinum ester with disulfide bond as theranostic nanoparticle for drug resistant tumor diagnosis and treatment

Vitamin E Poly(ethylene glycol) monoplatinum ester (TPGS) nanoparticles have attracted much attention in recent years for overcome multidrug resistance. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked polymer (FA-SS-TPGS) was synthesized. These polymer nanoparticles were utilized as theranostic agents for tumor-targeted magnetic resonance imaging (MRI) and chemotherapy. By loading doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) particles into TPGS nanoparticles, FA-SS-TPGS@DOX/SPIO nanoparticles are obtained. In vitro drug release studies revealed that under a reducing environment in the presence of glutathione (GSH), approximately 100% of the doxorubicin (DOX) was released from the disulfide bond-linked theranostic nanoparticles within 24 h. DOX and SPIO were efficiently delivered into HepG2-ADM cells due to the folate receptor-mediated endocytosis process of the nanoparticles. Additionally, the presence of glutathione (GSH) triggered the cleaving of the disulfide bonds, further facilitating the delivery of DOX and SPIO into the cells. Furthermore, the FA-SS-TPGS @DOX-SPIO nanoparticles exhibited strong MRI contrast enhancement properties. In conclusion, FA-SS-TPGS@DOX/SPIO are potential nanoparticles for tumor-targeted MRI and chemotherapy, which can also overcome multidrug resistance.

Fluorescent folic acid-chitosan/carbon dot for pH-responsive drug delivery and bioimaging

Nowadays, one of the most important reasons of death in the world is cancer. With the development of nanotechnology, advanced methods for treatment of cancer have introduced.In this work, the fluorescent carbon dots (CDs) were prepared from chitosan as the second abundant polysaccharide present in the nature. The surface of CDs was modified with chitosan (CDs/CS) and then the amino groups of chitosan were conjugated with activated folic acid (CDs/CS-FA) for controlled delivery of doxorubicin (DOX) as anticancer drug against HeLa cancer cells. The DOX loading efficiency of fluorescent CDs/CS-FA was high and nearly 60 %. Due to pH sensitive swelling/deswelling of CS, the percentage of cumulative DOX release could reach 90 % at cancer tissue (pH of 5.0) and 52 % at normal tissue (pH of 7.4) within 30 h. The cytotoxicity study revealed that the synthesized CDs were highly compatible on HeLa cells with cell viability 97–88 %. Cellular imaging shows that the entry of CDs/CS-FA to HeLa cells causes a green fluorescence, while the CDs/CS without FA have a negligible fluorescence. These results are due to the important role of FA in cell internalization. Thus, the CDs/CS-FA nanocarrier is suitable candidate for controlled pH sensitive drug delivery and cellular imaging.