Incorporation of chemotherapeutic agent and photosensitizer in a low temperature-sensitive liposome for effective chemo-hyperthermic anticancer activity

Objectives: In this study, we combined chemo- and hyperthermia therapy in a low temperature-sensitive liposome (LTSL) for potential cancer treatment.

Methods: Docetaxel (DOC) and indocyanine green (ICG) as a therapeutic agent and photosensitizer, respectively, were incorporated in a low temperature-sensitive liposome (LTSL/DI). Nanoparticles were evaluated for the physicochemical characterizations, in vitro uptake and cytotoxicity, and furthermore in vivo anticancer activity.

Results: The particle size of LTSL/DI was 130.8 ± 2.3 nm, and its drug release profile was pH- and temperature-dependent, which are effective for tumor targeting. The in vitro anticancer activity of LTSL/DI was significantly enhanced compared with free DOC in SCC-7 and MCF-7 cell lines. Interestingly, near-infrared laser irradiation after the treatment resulted in better anticancer activity than in the non-irradiated condition. The in vivo tumor regression effect of LTSL/DI in combination with NIR irradiation was much greater compared with the control group in SCC-7 tumor-bearing mice. After intratumoral injection of LTSL/DI, local heat induced by NIR irradiation and the localized docetaxel burst release could completely ablate the tumor, and inhibit its recurrence.

Conclusions: These results suggest LTSL/DI formulation as a potential therapeutic strategy with effectively localized anti-tumor activity and low risk of side effect to non-target organs.     

The efficacy of WGA modified daunorubicin anti-resistant liposomes in treatment of drug-resistant MCF-7 breast cancer

Background: Breast cancer is the most common malignancy and remains a leading cause of cancer-related deaths in female. Chemotherapy failure of breast cancer is mainly associated with multidrug resistance of cancer cells.

Purpose: The WGA modified daunorubicin anti-resistant liposomes were developed for circumventing the multidrug resistance and eliminating cancer cells.

Methods: WGA was modified on liposomal surface for increasing the intracellular uptake. Tetrandrine was inserted into the phospholipid bilayer for reversing cancer drug-resistance, and daunorubicin was encapsulated in liposomal aqueous core as an anticancer agent. Evaluations were performed on MCF-7 cells, MCF-7/ADR cells and xenografts of MCF-7/ADR cells.

Results: In vitro results showed that WGA modified daunorubicin anti-resistant liposomes exhibited suitable physicochemical properties, significantly increased intracellular uptake in both MCF-7 cells and MCF-7/ADR cells, and circumvented the multidrug resistance via inhibiting P-gp. In vivo results demonstrated that the targeting liposomes showed a long-circulatory effect in blood system, and could remarkably accumulate at the tumor location. The involved action mechanisms for the enhanced anticancer efficacy were activation of pro-apoptotic proteins (Bax and Bok), apoptotic enzymes (caspase 8, caspase 9 and caspase 3).

Conclusion: The established WGA modified daunorubicin anti-resistant liposomes could provide a potential strategy for treating resistant MCF-7 breast cancer.     

Paclitaxel nanosuspensions for targeted chemotherapy – nanosuspension preparation,characterization, and use

Abstract

Objective: The purpose of this work was to prepare a stable paclitaxel nanosuspension and test it for potential use as a targeted chemotherapeutic. Different particle coatings were employed to assess their impact on cellular uptake in vitro. In vivo work was then performed to demonstrate efficacy in tumor-bearing mouse models.

Materials and method: Paclitaxel nanosuspensions were prepared using a homogenization process and coated with excipients. Surface charge was measured by zeta potential, potency by high-performance liquid chromatography, and solubility using an in-line UV probe. Cellular uptake studies were performed via flow cytometry. In vivo experiments were performed to determine residence time, maximum tolerated dose, and the efficacy of paclitaxel nanosuspensions (Paclitaxel-NS).

Results: A stable paclitaxel nanosuspension was prepared and coated with various excipients. Studies in mice showed that the nanosuspension was well-tolerated and at least as effective as the IV Taxol control in prolonging mouse survival in a head and neck cancer model as well as an ovarian cancer model with a lower overall drug dose than the traditional IV administration route.

Conclusions: The paclitaxel nanosuspension is suitable for cellular uptake. The nanosuspension was effective in prolonging life in two separate xenograft orthotopic murine cancer models through two separate routes of administration.     

川芎嗪查尔酮类化合物的合成及其体外抗乳腺癌活性研究

目的设计、合成川芎嗪查尔酮类化合物并研究其抗乳腺癌活性。方法以盐酸川芎嗪为原料,通过酸碱中和、单氧化、重排、水解和醇羟基氧化制得重要中间体3,5,6-三甲基吡嗪-2-甲醛,再与芳乙酮发生Claisen-Schmidt羟醛缩合反应合成川芎嗪查耳酮类化合物,接着用BBr_3进行脱甲基得到了川芎嗪羟基查耳酮,并采用MTT法对目标化合物进行体外抗乳腺癌活性研究。结果合成了21个川芎嗪查尔酮类化合物,其结构均通过~1H-NMR和MS确证。生物活性结果测试表明,目标化合物对乳腺癌MCF-7和MDA-MB-231细胞均有较强抑制活,并对MDA-MB-231细胞有更强的选择抑制。其中查尔酮单元为二茂铁的衍生物9t对MCF-7和MDA-MB-231展现出了最强的抑制活性;同时,这些川芎嗪查尔酮类化合物对正常乳腺上皮细胞MCF-10A均没有毒性。结论查尔酮是一个重要的抗肿瘤药效团,能够提高川芎嗪的抗肿瘤活性,为今后发展新型、高效、低毒的具有抗肿瘤活性的川芎嗪衍生物提供了新思路。     

Evaluation of in vitro antioxidant,anticancer and in vivo antitumour activity of Termitomyces clypeatus MTCC 5091

Context: Termitomyces clypeatus (Lyophyllaceae) is a filamentous edible mushroom, having ethnomedicinal uses. However, information about the antioxidant, anticancer and antitumour properties of this mushroom remains to be elucidated.

Objective: The study examines the in vitro antioxidant, anticancer and in vivo antitumour activity of T. clypeatus.

Materials and methods: Antioxidant activity was evaluated with seven in vitro assays. Cytotoxicity of T. clypeatus was tested against a panel of cancer cells lines including U373MG, MDA-MB-468, HepG2, HL-60, A549, U937, OAW-42 and Y-79 using MTT assay. The antitumour activity of aqueous extract was evaluated against Ehrlich ascites carcinoma (EAC) tumour model in Swiss albino mice.

Results: HPLC analysis of aqueous extract revealed the presence of sugar entities. Termitomyces clypeatus showed excellent in vitro antioxidant activity. Termitomyces clypeatus was found cytotoxic against all cancer cells, among which it showed higher activity against U937 (IC₅₀ 25?±?1.02?μg/mL). Treatment of EAC-bearing mice with varied doses of aqueous extract significantly (p?<?0.01) reduced tumour volume, viable tumour cell count and improved haemoglobin content, RBC count, mean survival time, tumour inhibition and % increase life span. The enhanced antioxidant status in treated animals was evident from the decline in the levels of lipid peroxidation, increased levels of glutathione, catalase and superoxide dismutase.

Discussion: The analyzed data indicate that the aqueous extract of T. clypeatus exhibits significant antitumour activity, which might be due to the antioxidant effects on EAC bearing hosts.

Conclusion: Termitomyces clypeatus possesses anticancer activity, valuable for application in food and drug products.     

Novel anticancer alkene lactone from Persea americana

Abstract

Context: Persea americana Mill (Lauraceae) root bark is used in ethnomedicine for a variety of diseases including cancer.

Objective: To isolate and characterize the chemical constituent in P. americana, and also to determine the anticancer property of a new alkene lactone from the root bark of P. americana.

Materials and methods: The MCF-7 cells were treated with different concentrations of the pure compound for 48?h. The percentage of cells in the various phases, online monitoring of metabolic changes and integrin receptor expression determined by flow cytometry.

Results: One novel alkene lactone (4-hydroxy-5-methylene-3-undecyclidenedihydrofuran-2 (3H)-one) (1) was isolated and characterized using 1D-NMR, 2D-NMR, infrared, UV and MS. At a concentration of 10?µg/mL, significant reduction of proliferation of MCF-7 was induced while MCF-12?A cell was significantly stimulated by 10?µg/mL. The IC₅₀ value for MCF-7 cells is 20.48?µg/mL. Lower concentration of 1 harbor no significant effect on either MCF-7 or MCF-12A. The apoptotic rates of MCF-7 cells were increased significantly. At the final concentration 10?µg/mL, up to 80% of all breast cancer cells were dead. On the non-tumorigenic cell line MCF-12A, the same concentrations (1 and 10?µg/mL) of compound 1 caused significant enhanced apoptotic rates. A total of 1?µg/mL of 1 caused a decrease of α4-, α6-, β1- and β3-integrin expression.

Conclusions: The compound caused a stimulatory effect on non-tumorigenic MCF-12A cells with respect to cell adhesion while tumorigenic MCF-7 cells detached continuously. This is the first report on the anticancer effects of this class of compound.     

A nanoparticulate drug-delivery system for glaucocalyxin A: formulation,characterization, increased in vitro,and vivo antitumor activity

Glaucocalyxin A (GLA) is a phytochemical component with multiple pharmacological activities; however, glaucocalyxin A's wider use has been restricted by its poor solubility. In this study, GLA nanosuspensions were prepared with precipitation-combined ultrasonication and were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), and differential scanning calorimetry (DSC). The GLA nanosuspensions were spherical with a smooth surface and a small size of 143?nm, the drug payload achieved 8.95%, and the maximum GLA concentration reached 1?mg/mL. The lyophilized powders for the GLA nanosuspensions were amorphous and displayed a biphasic drug release pattern with an initial burst release and a consequent sustained release. In contrast to the free drug solution, GLA nanosuspensions showed higher in vitro antitumor activity against HepG2 cells (IC₅₀ value of 1.793 versus 2.884?μg/mL at 24?h, p?<?0.01). Meanwhile, nanosuspensions displayed better anticancer efficacy than free GLA on H22 bearing mice (54.11% versus 36.02% tumor inhibition rate). These results indicate that GLA nanosuspensions have great potential for the treatment of hepatic cancer.     

Investigation of the cytocidal potential of Rhinella jimi skin methanol extracts

Context: Amphibian skins have wide variety of biologically active compounds associated with the natural defenses of these animals.

Objectives: To study the in vitro anticancer activity of methanol extracts of the skin of Rhinella jimi Stevaux (Anura: Bufonidae).

Material and methods: The extract was obtained by cold methanol extraction for 96 h using dried skins (295 mg). The methanol skin extract was dried under reduced pressure, giving a 5.5% yield. In order to test for growth-inhibitory activity, in vitro tests were performed with the following cancer cell lines using concentrations ranging between 0.25–250 µg/mL of the extract by 48 h: K562 (leukemia), MCF-7 (breast), NCI-ADR (breast with MDR phenotype), UACC-62 (melanoma), NCI460 (lung), PCO3 (prostate), HT-29 (colon), OVCAR (ovary), and 786-0 (kidney).

Results: The methanol extract of R. jimi produced a growth inhibition in a dose-dependent manner against the most of the assayed cell lines. In addition to the growth inhibition, the extract induced the cell death in the ovary and colon lines (EC₅₀ 0.125 and 0.2 µg/mL, respectively), demonstrating 100% of inhibition with 2.5 µg/mL. However, prostate and leukemia cell lines demonstrated less sensitivity, with EC₅₀ of 24 and 235 µg/mL, respectively. This is the first report about the anticancer activity by natural products from the skin of R. jimi.

Conclusions: The methanol extracts of R. jimi significantly affected the growth of several cell lines, demonstrating that these compounds are a potential source of substances that could be utilized in cancer treatments.     

Increased brain uptake of docetaxel and ketoconazole loaded folate-grafted solid lipid nanoparticles

Docetaxel is used in the treatment of many types of cancer, but its entry into the brain is restricted by p-glycoprotein (p-gp) efflux. A potential drug–drug interaction exists between docetaxel and ketoconazole because both agents are metabolized hepatically by the cytochrome P-450 system, and ketoconazole can inhibit p-gp efflux of docetaxel at blood brain barrier. Hence, these two drugs were loaded in solid lipid nanoparticles (SLNPs) and surface of these NPs were modified with folic acid for brain targeting. These NPs were characterized for particle size, zeta potential, entrapment efficiency, in vitro drug release, cytotoxicity, and cell uptake in brain endothelial cell lines. Plasma and brain pharmacokinetics have shown increased brain uptake of docetaxel with surface-modified dual drug-loaded SLNPs. Brain permeation coefficient (K_in) of folate-grafted docetaxel and ketoconazole loaded SLNPs was 44 times higher than that of Taxotere. Hence, these NPs were suitable for the delivery of lipophilic anticancer drugs to the brain.From the Clinical EditorIn this paper, successful delivery of docetaxel and ketoconazole is reported using solid lipid nanoparticles surface modified with folic acid for brain targeting, which may pave the way to optimized clinical applications of lipophilic anticancer drugs to the brain.     

Tissue distribution of 2-methoxyestradiol nanosuspension in rats and its antitumor activity in C57BL/6 mice bearing lewis lung carcinoma

The purpose of the present study was to evaluate the tissue distribution and antitumor activity of 2-methoxyestradiol (2-ME) nanosuspension compared with 2-ME solution both in vitro and in vivo. 2-ME nanosuspension was made by nanoprecipitation-high-frequency ultrasonication method with the particle size of 168.4?±?3.2?nm and the zeta potential of ?29.79?±?1.89 mV. The overall targeting efficiency (TE^Q) of 2-ME nanosuspension was improved from 28.71 to 51.95% in the lung of rats. MTT assay showed that 2-ME nanosuspension could significantly enhance the in vitro cytotoxicity against lewis lung carcinoma (LLC) cells compared with the 2-ME solution, the IC₅₀ at 72?h was reduced from 6.35 µM for 2-ME solution to 3.56 µM for 2-ME nanosuspension. The antitumor activity in vivo was investigated in C57BL/6 mice bearing LLC, and the results indicated that 2-ME nanosuspension not only exhibited significant suppression of the tumor growth when compared with that of positive group or cyclophosphamide group at the same dose, but also enhanced the spleen indices. Overall, 2-ME nanosuspension could mainly deliver the drug to lungs and made the drug accumulate in the lungs, so 2-ME nanosuspension has a possible lung cancer therapeutic potential.     

Correlation Between Antioxidative Power and Anticancer Activity in Herbs from Traditional Chinese Medicine Formulae with Anticancer Therapeutic Effect

Abstract

Lobeliae chinensis. Herba (“ban bian lian”), Rheum officinale. Baill. (“da huang”), Sanguisorba officinalis. Linn. (“di yu”), Agrimonia pilosa. Ledeb. (“xian he cao”), and Paris polyphylla. Smith (“zhi hua tou”) are well-known traditional Chinese medicines. They are commonly used in traditional Chinese medicine formulae against cancer. In this study, the antioxidant and anticancer effects of water extracts of these herbs were investigated. In the antioxidant and anticancer studies, water extracts of di yu, xian he cao, and da huang were show to be the most antioxidative and had the highest growth inhibitory effect on human lung adenocarcinoma A549 cell and human breast cancer MCF-7 cell. By comparing their percentage free radical scavenging capacity (SR%) and percentage growth inhibition on A549 and MCF-7 cells, a positive linear relationship between antioxidant activity and anticancer effect of the five herbal water extracts was found. This suggested that the antioxidants of the herbal water extracts might contribute to their anticancer effects on A549 and MCF-7 cells.     

Emodin induces cytotoxic effect in human breast carcinoma MCF-7 cell through modulating the expression of apoptosis-related genes

Abstract

Context: The poor prognostic outcome of breast cancer is largely due to its resistance to cancer therapies. Development of therapeutic agents that can inhibit growth and induce apoptosis in breast cancer cells can help solve the problem. Emodin is an active anthraquinone that has been reported to have diverse biological effects.

Objective: In this study, the anticancer effects of emodin on growth inhibition, apoptosis induction and the expression of apoptosis-related genes in MCF-7 cells were investigated.

Materials and methods: Growth inhibition induced by emodin was investigated by the MTS assay and the colony formation assay; while emodin-induced apoptosis was determined by the COMET assay and DNA fragmentation detection. Emodin (35?μM)-induced alterations in the expression of apoptotic-related genes were detected by using real-time PCR.

Results: Emodin had significant growth inhibitory effects on MCF-7 cells with IC₅₀?=?7.22?µg/ml (～30?μM). It also exerted a concentration-dependant inhibitory effect on the colony-forming ability of MCF-7 cells with IC₅₀?=?7.60?µg/ml (～30?µM). Hallmarks of apoptosis, such as single-strand DNA breakage and DNA fragmentation, were observed in emodin-treated MCF-7 cells. The gene expression of Fas ligand (FASL) was up-regulated (p?<?0.01) but those of MCL1, CCND1 and C-MYC were down-regulated (p?<?0.05) in emodin-treated MCF-7 cells.

Discussion and conclusion: This study indicated that emodin could induce growth inhibition and apoptosis in MCF-7 cells through the modulation of the expression of apoptosis-related genes. The growth inhibitory effects of emodin might involve both the intrinsic and the extrinsic apoptotic pathways and cell cycle arrest.     

Formulation,optimisation and in-vitro,in-vivo evaluation of surfactant stabilised nanosuspension of Ginkgo biloba

Abstract

The purpose of this research work was to formulate the stable nanosuspension of Ginkgo biloba to increase its oral bioavailability. To achieve this goal, initially nanosuspensions of G. biloba were prepared with six different stabilisers. Afterwards, other formulation conditions were optimised with response surface methodology. Stabiliser screening study selected sodium lauryl sulphate as stabiliser to formulate the nanosuspension of G. biloba by antisolvent precipitation method. Under suggested optimal conditions of software, nanosuspension of G. biloba with mean particle size 139.5?nm, polydispersity index 0.258 and zeta potential 58.7?mV was prepared. Atomic force microscopy showed sheet like shape and very well distribution of G. biloba nanoparticles with approximate height of 15–30nm. Optimised nanosuspension of G. biloba demonstrated greater in-vitro dissolution and more plasma concentration of quercetin in G. biloba nanosuspension administrated rats in comparison to coarse suspension. Moreover, cytotoxicity study revealed no toxic effects of formulated nanosuspension.     

High drug payload curcumin nanosuspensions stabilized by mPEG-DSPE and SPC: in vitro and in vivo evaluation

Context: Curcumin (CUR) is a promising drug candidate based on its broad bioactivities and good antitumor effect, but the application of CUR is potentially restricted because of its poor solubility and bioavailability.

Objective: This study aims at developing a simple and effective drug delivery system for CUR to enhance its solubility and bioavailability thus to improve its antitumor efficacy.

Materials and methods: Curcumin nanosuspensions (CUR-NSps) were prepared by precipitation-ultrasonication method using mPEG2000-DSPE and soybean lecithin as a combined stabilizer.

Results: CUR-NSps with a high drug payload of 67.07% were successfully prepared. The resultant CUR-NSps had a mean particle size of 186.33?±?2.73?nm with a zeta potential of ?19.00?±?1.31?mV. In vitro cytotoxicity assay showed that CUR-NSps exhibited enhanced cytotoxicity compared to CUR solution. The pharmacokinetics results demonstrated that CUR-NSps exhibited a significantly greater AUC_0–24 and prolonged MRT compared to CUR injections after intravenous administration. In the biodistribution study, CUR-NSps demonstrated enhanced biodistribution compared with CUR injections in liver, spleen, kidney, brain, and tumor. The CUR-NSps also showed improved antitumor therapeutic efficacy over the injections (70.34% versus 40.03%, p?Conclusions: These results suggest that CUR-NSps might represent a promising drug formulation for intravenous administration of CUR for the treatment of cancer.     

Polyunsaturated fatty acid-based targeted nanotherapeutics to enhance the therapeutic efficacy of docetaxel

Since breast cancer is one of the most lethal malignancies, targeted strategies are urgently needed. In this study, we report the enhanced therapeutic efficacy of docetaxel (DTX) when combined with polyunsaturated fatty acids (PUFA) for effective treatment of multi-resistant breast cancers. Folic acid (FA)-conjugated PUFA-based lipid nanoparticles (FA-PLN/DTX) was developed. The physicochemical properties, in vitro uptake, in vitro cytotoxicity, and in vivo anticancer activity of FA-PLN/DTX were evaluated. FA-PLN/DTX could efficiently target and treat human breast tumor xenografts in vivo. They showed high payload carrying capacity with controlled release characteristics and selective endocytic uptake in folate receptor-overexpressing MCF-7 and MDA-MB-231 cells. PUFA synergistically improved the anticancer efficacy of DTX in both tested cancer cell lines by inducing a G2/M phase arrest and cell apoptosis. Combination of PUFA and DTX remarkably downregulated the expression levels of pro-apoptotic and anti-apoptotic markers, and blocked the phosphorylation of AKT signaling pathways. Compared to DTX alone, FA-PLN/DTX showed superior antitumor efficacy, with no signs of toxic effects in cancer xenograft animal models. We propose that PUFA could improve the therapeutic efficacy of anticancer agents in cancer therapy. Further studies are necessary to fully understand these findings and achieve clinical translation.     

1,3-二羟基异丙氧基-琥珀酸-8-莪术醇酯纳米混悬剂的制备及其性能研究

目的制备1,3-二羟基异丙氧基-琥珀酸-8-莪术醇酯纳米混悬剂(Cur-p-NS),并考察其一般特性、载药量和体外释放特性。方法采用超声–溶剂沉淀法制备Cur-p-NS,考察其粒度大小,多聚分散系数和Zeta电位。结果 Cur-p-NS的平均粒径为162.60±2.12 nm,多分散系数为0.182±0.002,Zeta电位为-24.60±8.97 m V,平均载药量为0.942 mg/mg,累积释放率可达到77%。结论 Cur-p-NS制备工艺简单和效果好,具有持续释放的特性。     

A nanoparticulate drug-delivery system for 20(S)-protopanaxadiol: formulation,characterization, increased oral bioavailability and anti-tumor efficacy

As with many other hydrophobic anticancer agents, 20(S)-protopanaxadiol (PPD) has a very low oral bioavailability. In this study, a precipitation-combined ultrasonication technique was used to prepare PPD nanosuspensions. The mean particle size of the nanosuspensions was approximately 222?±?12?nm, the drug payload achieved 50% after lyophilization and the maximum PPD concentration can reach 100?mg/ml, which is over 30?000 times the solubility of PPD in aqueous solution (3?μg/ml). After oral administration, the C_max and AUC_last values of PPD nanosuspensions were approximately 3.66-fold and 3.48-fold as those of PPD coarse suspensions, respectively. In contrast to the free drug solution, PPD nanosuspensions showed higher in vitro anti-tumor activity against HepG-2 cells (an IC₅₀ value of 1.40 versus 5.83?μg/ml at 24?h, p?<?0.01). The in vivo study in H22-tumor-bearing mice demonstrated that PPD nanosuspensions showed good anti-tumor efficacy with an inhibition rate of 79.47% at 100?mg/kg, while 50?mg/kg of cyclophosphamide was displayed as positive control, and the inhibition rate was 87.81%. Considering the highest drug payload, oral bioavailability reported so far, significant anti-tumor efficacy and excellent safety of encapsulated drugs, PPD nanosuspensions could be used in potential effective strategies for anticancer therapy; further investigation is ongoing.     

Taxane anticancer agents: a patent perspective

Introduction:Paclitaxel and docetaxel were two epoch-making anticancer drugs and have been successfully used in chemotherapy for a variety of cancer types. In the year 2010, a new taxane, cabazitaxel, was approved by FDA for use in combination with prednisone for the treatment of metastatic hormone-refractory prostate cancer. Albumin-bound paclitaxel (nab?-paclitaxel; abraxane) nanodroplet formulation was another notable invention (FDA approval 2005 for refractory, metastatic, or relapsed breast cancer). Abraxane in combination with gemcitabine for the treatment of pancreatic cancer was approved by FDA in 2013. Accordingly, there have been a huge number of patent applications dealing with taxane anticancer agents in the last 5 years. Thus, it is a good time to review the progress in this area and find the next wave for new developments.

Area covered: This review covers the patent literature from the year 2010 to early 2015 on various aspects of taxane-based chemotherapies and drug developments.

Expert opinion: Three FDA-approved taxane anticancer drugs will continue to expand their therapeutic applications, especially through drug combinations and new formulations. Inspired by the success of abraxane, new nano-formulations are emerging. Highly potent new-generation taxanes will play a key role in the development of efficacious tumor-targeted drug delivery systems.     

Formulation and dosage of therapeutic nanosuspension for active targeting of docetaxel (WO 2014210485A1)

Non-specificity and drug resistance are two major limitations of all chemotherapeutic agents. Ligand-conjugated nanomedicine is the most versatile approach for targeted cancer therapy. Attaching a targeting ligand to the nanoparticle surface increases drug concentration at the desired sites, decreases the dose needed and lessens side effects. The subject of this patent evaluation describes the preparation of a therapeutic nanosuspension of an anticancer drug, docetaxel (DTX). The nanoparticle matrix comprised a polylactic acid-polyethylene glycol block copolymer (PLA-PEG). The nanoparticles were actively directed towards prostate-specific membrane antigen (PSMA) over-expressing cancer cells using a targeting ligand S,S-2-{3-[1-carboxy-5-amino-pentyl-]ureido}-pantanedioic acid (GL2). The dose-limiting toxicity and maximum tolerated dose were determined for GL2-conjugated and DTX-loaded polymeric nanosuspensions. The efficacy of nanosuspensions was evaluated in people with various cancer types. The investigators claim the method of preparation of therapeutic nanosuspension, optimized composition of the formulation and dosage regimen for the clinical studies to effectively treat gastroesophageal and breast cancers.