Nanocarrier System For Delivery Research Articles

Aptamer-functionalized hybrid nanoparticle for the treatment of breast cancer

PurposeResistance to chemotherapeutic agents such as doxorubicin is a major reason for cancer treatment failure. At present the treatment option for metastatic breast cancer is very poor. Therefore, development of an effective therapeutic strategy to circumvent MDR of metastatic breast cancer is highly anticipated. The MDR of metastatic breast cancer cells was accompanied with the overexpression of P-gp transporter. Even though the overexpression of P-gp could be minimized by silencing with siRNA, the question is how they can be selectively targeted to the cancer cells. We propose that aptamer surface labeling of the nanoparticles could enhance the selectively delivery of p-gp siRNA into the metastatic breast cancer cells. Our hypothesis is that conjugating nanoparticles with a cancer cell specific aptamer should allow selective delivery of therapeutic drugs to tumor cells leading to enhanced cellular toxicity and antitumor effect as compared to unconjugated nanoparticles. The primary objective of this study is to develop a targeted nanocarrier delivery system for siRNA into breast cancer cells. Design methodsFor targeted delivery, Aptamer A6 has been used which can bind to Her-2 receptors on breast cancer cells. For aptamer binding to particle surface, maleimide-terminated PEG-DSPE (Mal-PEG) was incorporated into the nanoparticles. Initially, three blank hybrid nanoparticles (i.e. F21, F31, and F40) out of nine different formulations prepared by high pressure homogenization (HPH) using different amount of DOTAP, cholesterol, PLGA or PLGA-PEG and Mal-PEG were chosen. Then protamine sulfate-condensed GAPDH siRNA (TRITC conjugated; red) or P-gp siRNA was encapsulated into those nanoparticles. Finally, the particles were incubated with aptamer A6 (FITC conjugated; green) for surface labeling. ResultsAptamer labeled-nanoparticles having PLGA are smaller in size than those having PLGA-PEG. Surface charge was reduced when the particles were labeled with aptamer. Cell transfection was increased significantly in Her-2 (+) SKBR-3 and 4T1-R cells but not in Her-2 poorly expressed MDA MB-231 and MCF-7 cells. The knockdown of P-gp was increased significantly when the particles were labeled with aptamer. No significant cellular toxicity was observed for any of these formulations. ConclusionThis preliminary study concludes that aptamer-functionalized hybrid nanoparticles could be used to deliver P-gp targeted siRNA into the breast cancer cells to overcome chemoresistance.

A combined approach of hollow microneedles and nanocarriers for skin immunization with plasmid DNA encoding ovalbumin.

The aim of this study was to investigate the use of different types of microneedles (MNs) and nanocarriers for in vitro skin permeation and in vivo immunization of plasmid DNA encoding ovalbumin (pOVA). In vitro skin permeation studies indicated that hollow MNs had a superior enhancing effect on skin permeation compared with solid MN patches, electroporation (EP) patches, the combination of MN and EP patches, and untreated skin. Upon using hollow MNs combined with nanocarriers for pOVA delivery, the skin permeation was higher than for the delivery of naked pOVA, as evidenced by the increased amount of pOVA in Franz diffusion cells and immunoglobulin G (IgG) antibody responses. When the hollow MNs were used for the delivery of nanocarrier:pOVA complexes into the skin of mice, they induced a stronger IgG immune response than conventional subcutaneous (SC) injections. In addition, immunization of mice with the hollow MNs did not induce signs of skin infection or pinpoint bleeding. Accordingly, the hollow MNs combined with a nanocarrier delivery system is a promising approach for delivering pOVA complexes to the skin for promoting successful immunization.

A Review on Potential of Proteins as an Excipient for Developing a Nano-Carrier Delivery System.

In neo-age research, nano-materials have emerged as potential tools for the revolution of diagnostic and therapeutic field because of their nano-scale effects, increased surface area-volume ratio, and other beneficial properties. For the last few decades, protein has been regarded as the most attractive and versatile natural bio-macromolecule among all of the available biopolymers. Protein is largely exploited as a nano-carrier system in the pharmaceutical industry due to its low cytotoxocity, biocompatibility, biodegradability, abundant renewable sources, significant attaching ability, clinically useful targeting, and site-specific efficient uptake. This review mainly emphasizes on the latest development and progress achieved in the utilization of protein as a nano-vehicle for a large number of therapeutics such as drugs, genes, hormones, enzymse, nutraceuticals, antibodies, peptides, etc. We also discuss the sources of protein materials, fabrication aspects, advantages, constraints, in vivo and in vitro studies and provide a comparative analysis between the different types of proteins as nano-carriers. The variation of the release pattern and molecular mechanism of the encapsulated molecule with respect to different protein types and various nano-structures are also highlighted here to explore the enormous promises of this novel approach.

Development of a laser-activated mesoporous silica nanocarrier delivery system for applications in molecular and genetic research.

Nanoparticles have revolutionized medical research over the last decade. One notable emerging area of nanomedicine is research developments in the reproductive sciences. Since increasing evidence indicates links between abnormal gene expression and previously unexplained states of infertility, there is a strong impetus to develop tools, such as nanoparticle platforms, to elucidate the pathophysiological mechanisms underlying such states. Mesoporous silica nanoparticles (MSNPs) represent a powerful and safe delivery tool for molecular and genetic investigations. Nevertheless, ongoing progress is restricted by low efficiency and unpredictable control of cargo delivery. Here, we describe for the first time, the development of a laser-activated MSNP system with heat-responsive cargo. Data derived from human embryonic kidney cells (HEK293T) indicate that when driven by a heat-shock promoter, MSNP cargo exhibits a significantly increased expression following infrared laser stimulus to stimulate a heat-shock response, without adverse cytotoxic effects. This delivery platform, with increased efficiency and the ability to impart spatial and temporal control, is highly useful for molecular and genetic investigations. We envision that this straightforward stimuli-responsive system could play a significant role in developing efficient nanodevices for research applications, for example in reproductive medicine.

A Reactive (1)O2 - Responsive Combined Treatment System of Photodynamic and Chemotherapy for Cancer.

The development of reactive oxygen species (ROS)-responsive drug delivery and drug release has gradually attracted much attention in recent years as a promising therapeutic strategy. Singlet oxygen (1O2) as the major ROS species is widely used in photodynamic therapy (PDT) of cancer. In the present study, we introduce a combined treatment using ROS-sensitive thioketal (TK) linkage as a linker between upconversion nanoparticles (UNs)-based PDT and doxorubicin (DOX)-based chemotherapy. UNs can not only play a role in PDT, but can also be used as a nanocarrier for drug delivery of DOX. Moreover, the products of 1O2 during PDT are able to cleave TK linker inducing the release of DOX which can further achieve the goal of chemotherapy. By using this 1O2-responsive nanocarrier delivery system, DOX can easily reach the tumor site and be accumulated in the nuclei to effectively kill the cancer cells, and therefore decreasing the side effects of chemotherapy on the body. Thus, PDT also has the function of controlling drug release in this combination treatment strategy. Compared with monotherapy, the combination of PDT with chemotherapy also possesses excellent drug loading capability and anticancer efficiency.

A Nanoplatform with Precise Control over Release of Cargo for Enhanced Cancer Therapy.

The development of a nanocarrier delivery system having both sufficient stability in blood circulation and a rapid drug release profile at target sites remains a major challenge in cancer therapy. Here, a multifunctional star-shaped micellar system with a precisely spatiotemporal control of releasing encapsulated agents is developed by mixing a photoinitiated crosslinking amphiphilic copolymer with a phenylboronic acid (PBA)-functionalized redox-sensitive amphiphilic copolymer for the first time. The combination of the functional polymers effectively resolves the contradiction that the micellar system cannot release the rapid drug release in cells when it possesses an extreme stability that is often required in blood circulation. In this system, the inner core polymers are photo-crosslinked, endowing a stable micelle matrix structure; the end groups of the hydrophilic segments are decorated with PBA ligands, providing an active targeting ability; disulfide bonds in the micellar matrix impart a redox-responsive trigger for the prompt intracellular release of drugs. As a result, with a relatively low DOX dosage (2 mg kg(-1) per injection) the in vivo antitumor effect on H22-bearing BALB/c mice shows that the micelles have a high therapeutic efficacy against solid tumors while minimal side effects against normal tissues.

Perylenediimide-cored cationic nanocarriers deliver virus DNA to kill insect pests

The narrow infection range of insect virus restricts its use for the control of broad range of pests. A cationic fluorescent nanocarrier delivery system was successfully applied to broaden the host range of an insecticidal virus DNA, which should contributes to the organic and green food production.

Encapsulation of Functional Lipophilic Food and Drug Biocomponents

Lipophilic biocomponents pose a real challenge to food and drug researchers because they have weak solubility in water and cannot be easily included into the food and drug matrix. Biomaterials with new functional properties, i.e. biodegradable, biocompatible and stimulus responsive, have been tested for the purpose of improving the solubility and bioavailability of lipophilic components in recent years. Also, high-performance micro- and nanotechnologies were involved. These were used to prepare microcapsules and nanocarriers with multiple applications in food industry and pharmacy. The micro- and nano-encapsulation of lipophilic components is used to increase and maintain solubility in physiological fluids or the food matrix, to improve bioavailability and to protect the bioactive compounds against the aggression of some factors such as pH, enzymes, temperature, light and oxygen. The microcapsule and nanocarrier delivery systems guarantee the controlled and targeted delivery of bioactive molecules, thus increasing the therapeutic potential of drugs, along with food safety and security. The purpose of this review is to synthesize the newest information about the lipophilic biocomponents’ encapsulation. The first part of the paper is devoted to data on the solubility and bioavailability of lipophilic components used for food and drug formulations. The second part deals with the main methods of lipophilic compounds encapsulation, evincing the preparation of nanoparticles with applicability in the food and drug industry.

Synthesis and evaluation of PEG-O-chitosan nanoparticles for delivery of poor water soluble drugs: Ibuprofen

Current methods for preparation of PEGylated chitosan have limitations such as harsh de protecting step and several purification cycles. In the present study, a facile new method for conjugating methoxy polyethylene glycol (mPEG) to chitosan under mild condition is introduced to improve water solubility of chitosan and control the release of poor water soluble drugs. The method consists of chitosan modification by grafting the C6 position of chitosan to mPEG which is confirmed by Fourier transformed-infrared (FT-IR) and proton nuclear magnetic resonance (1HNMR) analyses. The amine groups at the C2 position of chitosan are protected using sodium dodecylsulfate (SDS) which is removed by dialyzing the precipitation against Tris solution. The chemical structure of the prepared polymer is characterized by FTIR and 1HNMR. The synthesized polymer is then employed to prepare nanoparticles which are characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), scanning electron microscopy (SEM), and dynamic light scattering (DLS) for their size and morphology. The nanoparticles are used for encapsulation of ibuprofen followed by in vitro release investigation in gastrointestinal and simulated biological fluids. The chitosan nanoparticles are used as control. The PEGylated nanoparticles show a particle size of 80nm with spherical morphology. The results clearly show that drug release from PEGylated chitosan nanoparticles is remarkably slower than chitosan. In addition, drug encapsulation and encapsulation efficiency in PEGylated nanoparticles are dependent on the amount of drug added to the formulation being significantly higher than chitosan nanoparticles. This study provides an efficient, novel, and facile method for preparing a nano carrier system for delivery of water insoluble drugs.

Synthesis and characterization of curcumin loaded polymer/lipid based nanoparticles and evaluation of their antitumor effects on MCF-7 cells

BackgroundHybrid materials are synthesized using hydrophilic polymer and lipids which ensure their long term systemic circulation through intravenous administration and enhance loading of hydrophobic drugs. The purpose of this study is to prepare, characterize and evaluate the in vitro efficacy of curcumin loaded poly-hydroxyethyl methacrylate/stearic acid nanoparticles in MCF-7. MethodsC-PSA-NPs, prepared using the emulsification–solvent evaporation method were characterized by dynamic laser scattering, SEM, AFM, FT-IR, X-ray diffraction, and TGA. The in vitro release behavior was observed in PBS pH7.4, the anticancer potential was analyzed by MTT assay, cell cycle and apoptosis studies were performed through flow cytometry. C-PSA-NPs drug localization and cancer cell morphological changes were analyzed in MCF-7 cell line. ResultsC-PSA-NPs exhibited the mean particle size in the range of 184nm with no aggregation. The surface charge of the material was around −29.3mV. Thermal studies (TGA) and surface chemistry studies (FT-IR, XRD) showed the existence of drug curcumin in C-PSA-NPs. The MTT assay indicated higher anticancer properties and flow cytometry studies revealed that there were better apoptotic activity and maximum localization of C-PSA-NPs than curcumin. ConclusionsPolymer lipid based drug delivery appeared as one of the advancements in drug delivery systems. Through the present study, a novel polymer lipid based nanocarrier delivery system loaded with curcumin was demonstrated as an effective and potential alternative method for tumor treatment in MCF-7 cell line. General significanceC-PSA-NPs exhibited potent anticancer activity in MCF-7 cell line and it indicates that C-PSA-NPs are a suitable carrier for curcumin.

Bioorthogonal, two-component delivery systems based on antibody and drug-loaded nanocarriers for enhanced internalization of nanotherapeutics

Nanocarriers play an important role in targeted cancer chemotherapy. The optimal nanocarrier delivery system should provide efficient and highly specific recognition of the target cells and rapid internalization of the therapeutic cargo to reduce systemic toxicity as well as to increase the cytotoxicity to cancer cells. To this end, we developed a two-step, two-component targeted delivery system based on antibody and drug-loaded nanocarrier that uses bioorthogonal click reactions for specific internalization of nanotherapeutics. The pretargeting component, anti-HER2 humanized monoclonal antibody, trastuzumab, functionalized with azide groups labels cancer cells that overexpress HER2 surface receptors. The drug carrier component, dibenzylcyclooctyne substituted albumin conjugated with paclitaxel, reacts specifically with the pretargeting component. These two components form cross-linked clusters on the cell surface, which facilitates the internalization of the complex. This strategy demonstrated substantial cellular internalization of clusters consisted of HER2 receptors, modified trastuzumab and paclitaxel-loaded albumin nanocarriers, and subsequent significant cytotoxicity in HER2-positive BT-474 breast cancer cells. Our results show high efficacy of this strategy for targeted nanotherapeutics. We foresee to broaden the applications of this strategy using agents such as radionuclides, toxins, and interfering RNA.

PH-responsive complexes using prefunctionalized polymers for synchronous delivery of doxorubicin and siRNA to cancer cells

A nanocarrier delivery system that can simultaneously deliver a chemotherapeutic drug and siRNA to the tumor is emerging as a promising treatment strategy for cancer treatment. In this study, a multifunctional PHD/PPF/siRNA complexes was developed by one-step assembly of prefunctionalized polymers: PEI–HZ–DOX (PHD) and PEI-PEG-Folate (PPF) with siRNA. The PHD, a conjugate of PEI (polyethylenimine) with doxorubicin (DOX) via a pH-responsive hydrazone linkage, enables pH-controlled drug release. The PPF, a tumor-targeting folate ligand conjugated to PEI using polyethyleneglycol (PEG) as a linker, enables immune evasion and cell-specific targeting. The prefunctionalized PHD and PPF as well as the self-assembly complexes reveals advantage on safety in further application for siRNA delivery. By exploiting distinct triple ratios of PHD, PPF and siRNA during nanocomplexes formulation, the folate surface density, DOX loading amount and siRNA complexation can be precisely and reproducibly changed. The studies showed that the complexes was capable of delivering siRNA and DOX to cancerous cells and release synchronously in cell by acid-triggered manner, i.e. hydrazone bond cleavage and endosome/lysosome escape using flow cytometry and confocal laser scanning microscopy analysis. The results highlight the potential for therapeutic gene silencing in vitro and in vivo using RT-PCR and non-invasive in vivo imaging systems. The PHD/PPF/siRNA complexes can increase DOX and siRNA accumulation in cancerous cells and decrease the nonspecific distribution in normal tissues by the combination of EPR effect of nanocarriers, pH-triggered drug release, folate-mediated targeted delivery, and synergistic action of DOX and siRNA.

Drug Delivery Using Nanocarriers: Indian Perspective

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Drug delivery technologies are patent protected formulation technologies that modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. Current efforts in the area of drug delivery include the development of targeted delivery in which the drug is only active in the target area of the body (for example, in cancerous tissues or other diseased tissues) and sustained release formulations in which the drug is released over a period of time in a controlled manner from a formulation. Nanocarrier delivery systems are extensively being investigated as a drug delivery strategy in the pharmaceutical research from the last 3 decades. Nanoparticulate technologies in general offer immense benefits such as solubilization of hydrophobic active pharmaceutical ingredient (API), improvement in bioavailability, improved (or altered) pharmacokinetics of API and protection of API from physical, chemical or biological degradation. As nanocarriers may also exert toxicological effects, nanotoxicology has emerged as a new branch of toxicology for studying undesirable effects of nanocarriers. Therefore, development of novel nanocarriers for therapeutics and diagnostics must proceed in tandem with assessment of any toxicological and environmental side effects of these carriers.

A Novel Nanocarrier Delivery System for Doxorubicin With Improved Tumor Response and Reduced Systemic Toxicity in Advanced Pediatric Non-Hodgkin Lymphoma

A Novel Nanocarrier Delivery System for Doxorubicin With Improved Tumor Response and Reduced Systemic Toxicity in Advanced Pediatric Non-Hodgkin Lymphoma

Effect of molecular weight of polyethyleneimine on loading of CpG oligodeoxynucleotides onto flake-shell silica nanoparticles for enhanced TLR9-mediated induction of interferon-α

BackgroundClass B CpG oligodeoxynucleotides primarily interact with Toll-like receptor 9 (TLR9) in B cells and enhance the immune system through induction of various interleukins including interleukin-6 in these immune cells. Although free class B CpG oligodeoxynucleotides do not induce interferon (IFN)-α production, CpG oligodeoxynucleotide molecules have been reported to induce IFN-α when loaded onto nanoparticles. Here, we investigated the in vitro induction of IFN-α by a nanocarrier delivery system for class B CpG oligodeoxynucleotide molecules.MethodsFor improving the capacity to load CpG oligodeoxynucleotide molecules, flake-shell SiO2 nanoparticles with a specific surface area approximately 83-fold higher than that of smooth-surfaced SiO2 nanoparticles were prepared by coating SiO2 nanoparticles with polyethyleneimine (PEI) of three different number-average molecular weights (Mns 600, 1800, and 10,000 Da).ResultsThe capacity of the flake-shell SiO2 nanoparticles to load CpG oligodeoxynucleotides was observed to be 5.8-fold to 6.7-fold higher than that of smooth-surfaced SiO2 nanoparticles and was found to increase with an increase in the Mn of the PEI because the Mn contributed to the positive surface charge density of the nanoparticles. Further, the flake-shell SiO2 nanoparticles showed much higher levels of IFN-α induction than the smooth-surfaced SiO2 nanoparticles. The highest IFN-α induction potential was observed for CpG oligodeoxynucleotide molecules loaded onto flake-shell SiO2 nanoparticles coated with PEI of Mn 600 Da, although the CpG oligodeoxynucleotide density was lower than that on flake-shell SiO2 nanoparticles coated with PEI of Mns 1800 and 10,000 Da. Even with the same density of CpG oligodeoxynucleotides on flake-shell SiO2 nanoparticles, PEI with an Mn of 600 Da caused a markedly higher level of IFN-α induction than that with Mns of 1800 Da and 10,000 Da. The higher TLR9-mediated IFN-α induction by CpG oligodeoxynucleotides on flake-shell SiO2 nanoparticles coated with a PEI of Mn 600 Da is attributed to residence of the CpG oligodeoxynucleotide molecules in endolysosomes.

Self-Assembling Peptides: Potential Role in Tumor Targeting

This review focuses on the application of two classes of peptides, i.e., self-assembling peptides (SAPs) and cell-targeting peptides (CTPs), in the development of nanocarrier delivery systems. Self-assembling peptides are emerging in a wide range of biomedical and bioengineering applications and fall into several classes, including peptide amphiphilies, bolaamphiphile peptides, cyclic peptides, and ionic complementary peptides, which can be found naturally or synthesized. The advantage of synthesizing peptides is that their self-assembling properties can be exploited to form desirable structures for various applications. Another, unique property of self-assembling peptides, is stimuli-responsibility in different environments including various pHs, temperatures, ionic strengths, etc. These characteristics make peptides applicable in a wide range of biomaterials in drug discovery. This study reviews the design principles of well-known self-assembling peptides, as well as their physical/chemical properties. In addition, it discusses the therapeutic cancer-targeting peptides and current combinatorial peptide library methods used to identify targeting peptides. Cancer-targeting peptides can target either tumor cell surfaces or tumor vasculature. The RGD peptide is one of the first tumor-targeting peptides that can bind to self-assembling peptides or any other nanocarrier to improve the therapeutic efficiency of targeting drug delivery systems.

Abstract 4439: A reversibly self-crosslinking nano-carrier system for efficient anticancer drug delivery

Abstract It is known that the intracellular concentration of glutathione (GSH) is substantially higher than that in the cellular exterior (∼10 mM vs ∼2 μM) and many types of tumor cells have an elevated GSH level compared to normal cells. This dramatic variation of the GSH concentration provides an opportunity for designing tumor specific drug delivery systems. Most of the chemotherapeutic drugs used in clinic suffer from severe dose-limiting side effects. In order to enhance the therapeutic efficacy and minimum the side effect of these drugs, we developed a stable and efficient nano-carrier drug delivery system based on the disulfide crosslinked micelles comprise of poly (ethylene glycol) (PEG) and dendritic oligmers of cholic acids and cysteines. Various poorly water-soluble anticancer drugs can be efficiently incorporated inside these polymeric nano-carriers. The nano-carriers are stabilized by disulfide bridges in the core to avoid premature release of the loaded drugs during circulation. After reaching the tumor sites via enhanced permeability and retention (EPR) effect, the nano-carriers will disassemble to release the core-loaded drugs upon the cleavage of disulfide bridges under reductive conditions following the intracellular uptake or triggered by additional reducing agents. The crosslinked nano-carriers were spherical with a uniform size of 30 ± 5 nm, and can load paclitaxel (PTX) in the core with drug loading content up to 35% (w/w). Cross-linking of the nano-carriers within the core reduced their critical aggregate concentration and greatly enhanced their stability in non-reductive physiological conditions. The release of PTX from the crosslinked nano-carriers was significantly slower than that from non-crosslinked nano-carriers and can be gradually facilitated in a reducing environment. The fluorescence intensity of BODIPY 650/665 (near infrared dye) labeled disulfide crosslinked nano-carriers sustained up to 24 hours within the blood stream of nude mice while that of non-crosslinked nano-carriers decreased faster and fell into the background level within 8 hours post injection. Targeted drug delivery to tumor site with these crosslinked nano-carriers was demonstrated by near infrared fluorescence imaging in nude mice bearing ovarian cancer xenograft. The nano-formulation of PTX was found to be less toxic than its free drug form in nude mice. We further demonstrated the crosslinked nano-formulation of PTX was more efficacious than both free drug and non-crosslinked nano-formulation of PTX in ovarian cancer xenograft model. This new class of nano-therapeutics shows great promise in the future cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4439. doi:10.1158/1538-7445.AM2011-4439

Encapsulation of hydrophobic anticancer drug in nano-scale porous ceramic materials for photodynamic therapy

A hydrophilic nano-scale porous ceramic material, silica nano-carrier, was prepared using microemulsion method to deliver hypocrellin A (HA), a hydrophobic photosensitive anti-cancer drug, to cancer cells in vitro. The result hypocrellin A encapsulated silica nano-carrier delivery systems (HA-SNDS) are spherical, highly monodispersed, stable in aqueous system and own high drug encapsulation ability. Irradiation of the HA-SNDS with light of suitable wavelength results in efficient generation of singlet oxygen; further more the photo-stability of HA-SNDS is superior to free HA. In aqueous medium, the fluorescence intensity of the entrapped drug is stronger than the free drug, permitting use of fluorescence mediated bioimaging studies. In addition, HA-SNDS was stable at a wide range of pH. In vitro studies have demonstrated the active uptake of HA-SNDS into the cytosol of tumor cells. Comparative studies with free HA and HA-SNDS have demonstrated that the in vitro PDT efficacy of encapsulated HA is obvious superior to free HA. All these properties of HA-SNDS could make it a promising candidate for photodynamic therapy.

A novel intralymphatic nanocarrier delivery system for cisplatin therapy in breast cancer with improved tumor efficacy and lower systemic toxicity in vivo

Background A lymphatically delivered nanoconjugate of cisplatin was evaluated in an orthotopic mouse model of locoregionally metastatic breast cancer (LABC) to determine if it can overcome some of the limitations of standard cisplatin therapy such as high systemic toxicity. Methods Human breast cancer cells (10 7 MDA-MB-468LN) were injected into the mammary fat pad of female nu/nu mice. Once tumor volume reached 50 mm 3, intravenous cisplatin or subcutaneous hyaluronan-cisplatin (HA-cisplatin) nanoconjugate was given 1/week × 3 weeks at 3.3 mg/kg (platinum basis). Results Nanoconjugates colocalized with the tumors after subcutaneous peritumoral injection and showed improved efficacy to intravenous cisplatin. After 1 month, renal tubular hemorrhage and edema were more prevalent in the intravenous formulation compared with subcutaneous HA-cisplatin nanoconjugates. Conclusions This nanocarrier delivery platform focuses on delivering drugs to the areas in which tumor burden is greatest, potentially reducing systemic toxicity, and has future applicability as a neoadjuvant or adjuvant therapy for LABC.