Refinement of safety and efficacy of anti-cancer chemotherapeutics by tailoring their site-specific intracellular bioavailability through transporter modulation.

Low intracellular bioavailability, off-site toxicities, and multi drug resistance (MDR) are the major constraints involved in cancer chemotherapy. Many anticancer molecules fail to become a good lead in drug discovery because of their poor site-specific bioavailability. Concentration of a molecule at target sites is largely varied because of the wavering expression of transporters. Recent anticancer drug discovery strategies are paying high attention to enhance target site bioavailability by modulating drug transporters. The level of genetic expression of transporters is an important determinant to understand their ability to facilitate drug transport across the cellular membrane. Solid carrier (SLC) transporters are the major influx transporters involved in the transportation of most anti-cancer drugs. In contrast, ATP-binding cassette (ABC) superfamily is the most studied class of efflux transporters concerning cancer and is significantly involved in efflux of chemotherapeutics resulting in MDR. Balancing SLC and ABC transporters is essential to avoid therapeutic failure and minimize MDR in chemotherapy. Unfortunately, comprehensive literature on the possible approaches of tailoring site-specific bioavailability of anticancer drugs through transporter modulation is not available till date. This review critically discussed the role of different specific transporter proteins in deciding the intracellular bioavailability of anticancer molecules. Different strategies for reversal of MDR in chemotherapy by incorporation of chemosensitizers have been proposed in this review. Targeted strategies for administration of the chemotherapeutics to the intracellular site of action through clinically relevant transporters employing newer nanotechnology-based formulation platforms have been explained. The discussion embedded in this review is timely considering the current need of addressing the ambiguity observed in pharmacokinetic and clinical outcomes of the chemotherapeutics in anti-cancer treatment regimens.

Implication of metabolomics and transporter modulation based strategies to minimize multidrug resistance and enhance site-specific bioavailability: a needful consideration toward modern anticancer drug discovery.

Induction of drug-metabolizing enzymes and efflux transporters (DMET) through activation of pregnane x receptor (PXR) is the primary factor involved in almost all bioavailability and drug resistance-related problems of anticancer drugs. PXR is a transcriptional regulator of many metabolizing enzymes and efflux transporters proteins like p-glycoprotein (p-gp), multidrug resistant protein 1 and 2 (MRP 1 and 2), and breast cancer resistant protein (BCRP), etc. Several anticancer drugs are potent activators of PXR receptors and can modulate the gene expression of DMET proteins. Involvement of anticancer drugs in transcriptional regulation of DMET can prompt increased metabolism and efflux of their own or other co-administered drugs, which leads to poor site-specific bioavailability and increased drug resistance. In this review, we have discussed several novel strategies to evade drug-induced PXR activation and p-gp efflux including assessment of PXR ligand and p-gp substrate at early stages of drug discovery. Additionally, we have critically discussed the chemical structure and drug delivery-based approaches to avoid PXR binding and inhibit the p-gp activity of the drugs at their target sites.

Biosimilars accessible in the market for the treatment of cancer.

Biosimilars are the biological product clinically identical to a biologic reference standard regarding their strength, purity, and safety. A large segment of biosimilars has been developed for the treatment of cancer. This review aims to discuss various facets of biosimilars and explicates on biosimilars accessible in the market for cancer clinical intervention. It also illustrates the outcomes of recent clinical trial studies concerning biosimilars. Further, it also crosstalk the safety profiles, regulatory approval requirements, and allied challenges therein. The work will be of significant interest to researchers working in the field of biologics and biosimilars.

Multifunctional polymeric micellar nanomedicine in the diagnosis and treatment of cancer.

Polymeric micelles are a prevalent topic of research for the past decade, especially concerning their fitting ability to deliver drug and diagnostic agents. This delivery system offers outstanding advantages, such as biocompatibility, high loading efficiency, water-solubility, and good stability in biological fluids, to name a few. The multifunctional polymeric micellar architect offers the added capability to adapt its surface to meet the looked-for clinical needs. This review cross-talks the recent reports, proof-of-concept studies, patents, and clinical trials that utilize polymeric micellar family architectures concerning cancer targeted delivery of anticancer drugs, gene therapeutics, and diagnostic agents. The manuscript also expounds on the underlying opportunities, allied challenges, and ways to resolve their bench-to-bedside translation for allied clinical applications.

Discovery of boronic acid-based potent activators of tumor pyruvate kinase M2 and development of gastroretentive nanoformulation for oral dosing.

Several studies have established that cancer cells explicitly over-express the less active isoform of pyruvate kinase M2 (PKM2) is critical for tumorigenesis. The activation of PKM2 towards tetramer formation may increase affinity towards phosphoenolpyruvate (PEP) and avoidance of the Warburg effect. Herein, we describe the design, synthesis, and development of boronic acid-based molecules as activators of PKM2. The designed molecules were inspired by existing anticancer scaffolds and several fragments were assembled in the derivatives. 6a-6d were synthesized using a multi-step synthetic strategy in 55-70% yields, starting from cheap and readily available materials. The compounds were selectively cytotoxic to kill the cancerous cells at 80 nM, while they were non-toxic to the normal cells. The kinetic studies established the compounds as novel activators of PKM2 and (E/Z)-(4-(3-(2-((4-chlorophenyl)amino)-4-(dimethylamino)thiazol-5-yl)-2-(ethoxycarbonyl)-3-oxoprop-1-en-1-yl) phenyl)boronic acid (6c) emerged as the most potent derivative. 6c was further evaluated using various in silico tools to understand the molecular mechanism of tetramer formation. Docking studies revealed that 6c binds to the PKM2 dimer at the dimeric interface. Further to ascertain the binding site and mechanism of action, rigorous MD (molecular dynamics) simulations were undertaken, which led to the conclusion that 6c stabilizes the center of the dimeric interface that possibly promotes tetramer formation. We further planned to make a tablet of the developed molecule for oral delivery, but it was seriously impeded owing to poor aqueous solubility of 6c. To improve aqueous solubility and retain 6c at the lower gastrointestinal tract, thiolated chitosan-based nanoparticles (TCNPs) were prepared and further developed as tablet dosage form to retain anticancer potency in the excised goat colon. Our findings may provide a valuable pharmacological mechanism for understanding metabolic underpinnings that may aid in the clinical development of new anticancer agents targeting PKM2.

Exosomes in multidrug-resistant cancer.

Multiple drug resistance (MDR) is a significant challenge in the treatment of cancer using chemotherapy. There are numerous reasons and mechanisms that are responsible for the development of MDR in cancer tissues. Further, exosomes and its constituents also play a vital role in limiting the efficacy of chemotherapeutic agents. Exosomes are well known for their role in developing resistance in addition to promoting tumor advancement and metastasis. This review discusses the role of exosomes in the development of drug resistance along with their allied mechanisms. This review also discusses the upregulation and downregulation of various exosomal components, which can be effectively employed as diagnostic biomarkers in the treatment of cancer. The essential applications of exosomes to treat drug-resistant cancer have also been discussed.

Green graphene nanoplates for combined photo-chemo-thermal therapy of triple-negative breast cancer.

Aim: Green graphene oxide (GO) nanoplates, which are reduced and stabilized by quercetin and guided by folate receptors (quercetin reduced and loaded GO nanoparticles-folic acid [FA]), were developed to mediate combined photo-chemo-thermal therapy of triple-negative breast cancer. Materials & methods: Modified Hummers method was used for the synthesis of GO followed by its reduction using quercetin, FA was then conjugated as a targeting ligand. A cytotoxicity assay, apoptosis assay and cellular uptake assay were performed in vitro in MDA-MB-231 cell line with and without irradiation of a near-infrared 808 nm laser. Results & conclusion: Quercetin reduced and loaded GO nanoparticles-FA showed significantly high cellular uptake (p < 0.001) and cytotoxic effects in MDA-MB-231 cells, which was even more prominent under the situation of near-infrared 808 nm laser irradiation, making it a potential option for treating triple-negative breast cancer.

Tumor microenvironment targeted nanotherapeutics for cancer therapy and diagnosis: A review.

Recent findings suggest that the cellular and extracellular materials surrounding the cancerous cells from an atypical tumor microenvironment (TM) play a pivotal role in the process of tumor initiation and progression. TM comprises an intricate system involving diverse cell types including endothelial cells, pericytes, smooth muscle cells, fibroblasts, various inflammatory cells, dendritic cells, and cancer stem cells (CSCs). The TM-forming cells dynamically interact with the cancerous cells through various signaling mechanisms and pathways. The existence of this dynamic cellular communication is responsible for creating an environment suitable for sustaining a reasonably high cellular proliferation. Presently, researchers are showing interest to use these TM conditions to mediate effective targeting measures for cancer therapy. The use of nanotherapeutics-based combination therapy; stimuli-responsive nanotherapeutics targeting acidic pH, hypoxic environment; and nanoparticle-induced hyperthermia are some of the approaches that are under intense investigation for cancer therapy. This review discusses TM and its role in cancer progression and crosstalk understanding, opportunities, and epigenetic modifications involved therein to materialize the capability of nanotherapeutics to target cancer by availing TM. STATEMENT OF SIGNIFICANCE: This article presents various recent reports, proof-of-concept studies, patents, and clinical trials on the concept of tumor microenvironment for mediating the cancer-specific delivery of nanotechnology-based systems bearing anticancer drug and diagnostics. We highlight the potential of tumor microenvironment; its role in disease progression, opportunities, challenges, and allied treatment strategies for effective cancer therapy by conceptual understanding of tumor microenvironment and epigenetic modifications involved. Specifically, nanoparticle-based approaches to target various processes related to tumor microenvironment (pH responsive, hypoxic environment responsive, targeting of specific cells involved in tumor microenvironment, etc.) are dealt in detail.

Dendrimer grafted albumin nanoparticles for the treatment of post cerebral stroke damages: A proof of concept study.

Stroke is the second largest disease of mortality. The biggest hurdle in designing effective brain drug delivery systems is offered by the blood-brain barrier (BBB), which is highly impermeable to many drugs. Albumin nanoparticles (NP) have gained attention due to their multiple ligand binding sites and long circulatory half-life. Citicoline (CIT) is reported to enhance the acetylcholine secretion in the brain and also helps in membrane repair and regeneration. However, the poor BBB permeation of CIT results in lower levels of CIT in the brain. This demands the development of a suitable delivery platform to completely realize the therapeutic benefit of CIT in stroke therapy. This investigation reports the synthesis and characterization of second generation (2.0 G) dendrimer Amplified Albumin (dAA) biopolymer by FTIR, MALDI-TOF, and surface charge (mV). Further, the synthesized biopolymer has been utilized to develop a CIT nanoformulation using a commercially translatable one-pot process. Release of CIT from biopolymer was performed within an acetate buffer at pH 5 and Phosphate buffer at pH 7.4. Further, we investigated the ability of biopolymer to permeate BBB by in vitro permeability assay in bEnd.3 cells. MTT assay of CIT-dAA-NP, CIT-ANP, and 2.0 G PAMAM dendrimers was performed in bEnd.3 cells. Therapeutic efficacy of the synthesized biopolymer was determined by VEGF gene expression within an in vitro hypoxia model in PC12 cells. Thus, this investigation resulted in biopolymers that can be used to deliver any therapeutic agent by altering the permeability of the BBB. Also, cationization by dendrimer grafting is one such strategy that may be used to cationize any other negatively charged polymer, such as albumin. The synthesized biopolymer is not limited to deliver molecules to the brain, but can also be used to increase the loading of negatively-charged drug molecules, siRNA, or any other oligonucleotide.

Exosomal miRNA in chemoresistance, immune evasion, metastasis and progression of cancer.

In the treatment of cancer, there are three significant limitations causing high mortality and recurrence rates among cancer patients. First, the escape of tumor cells from the immune system; second, the development of multi-drug resistance (MDR) to chemotherapeutic drugs; and, third, the noxious metastases of cancer cells. Exosomes are vesicular cargos involved in the transportation of miRNA, mRNA and proteins from one cell to another cell. This review details the current understanding of the exosomal transmission of miRNA and crosstalk with the downstream consequences, ultimately leading to the progression and metastasis of cancer. Further, this review also discusses how exosomal miRNA can provide promising novel targets for the treatment and detection of cancer.

Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer.

In tumorous tissues, the absence of vasculature supportive tissues intimates the formation of leaky vessels and pores (100 nm to 2 µm in diameter) and the poor lymphatic system offers great opportunity to treat cancer and the phenomenon is known as Enhanced permeability and retention (EPR) effect. The trends in treating cancer by making use of EPR effect is increasing day by day and generate multitudes of possibility to design novel anticancer therapeutics. This review aimed to present various factors affecting the EPR effect along with important things to know about EPR effect such as tumor perfusion, lymphatic function, interstitial penetration, vascular permeability, nanoparticle retention etc. This manuscript expounds the current advances and cross-talks the developments made in the of EPR effect-based therapeutics in cancer therapy along with a transactional view of its current clinical and industrial aspects.

Functionalized carbon nanotubes as emerging delivery system for the treatment of cancer.

In recent time, carbon nanotubes (CNTs) have gained vital importance for pharmaceutical formulation scientist for delivering drugs and genes, owing to their excellent surface properties. For example, their aspect ratio is thought to be responsible for their excellent cell penetration aptitude; anisotropic conductivity/semi-conductivity along their axis is ideal for integration with nervous and muscular tissue; an ultrahigh surface area maximizes their ability to "talk" with biological matter; the hollow interior provides an enormous cargo-carrying capacity for drug delivery; and their exteriors are readily functionalized to permit tailoring of solubility and biological recognition. Despite their immense capabilities for the delivery of drugs, genes and other biomedically essential materials, there use is restricted primarily because of the severe toxicity. However, the reactive nature of the surface of the CNTs allowed attaching the guest molecules (drug, siRNA, and diagnostics) of interest which helps in increasing the biocompatibility of these novel nanocarriers. As per the need, CNTs can be modified with peptides, organic molecules, carbohydrates, polymers and used mainly for cancer targeting and tumor cell accumulation. This review expounds different functionalization strategies employed for CNTs that created new opportunities for scientists to improve the potential of delivered therapeutics.

Targeting luteinizing hormone-releasing hormone: A potential therapeutics to treat gynecological and other cancers.

Cancer is a prime healthcare problem that is significantly responsible for universal mortality. Despite distinguished advancements in medical field, chemotherapy is still the mainstay for the treatment of cancers. During chemotherapy, approximately 90% of the administered dose goes to normal tissues, with mere 2-5% precisely reaching the cancerous tissues. Subsequently, the resultant side effects and associated complications lead to dose reduction or even discontinuance of the therapy. Tumor directed therapy therefore, represents a fascinating approach to augment the therapeutic potential of anticancer bioactives as well as overcomes its side effects. The selective overexpression of LHRH receptors on human tumors compared to normal tissues makes them a suitable marker for diagnostics, molecular probes and targeted therapeutics. These understanding enabled the rational to conjugate LHRH with various cytotoxic drugs (doxorubicin, DOX; camptothecin etc.), cytotoxic genes [small interfering RNA (siRNA), micro RNA (miRNA)], as well as therapeutic nanocarriers (nanoparticles, liposomes or dendrimers) to facilitate their tumor specific delivery. LHRH conjugation enhances their delivery via LHRH receptor mediated endocytosis. Numerous cytotoxic analogs of LHRH were developed over the past two decades to target various types of cancers. The potency of LHRH compound were reported to be as high as 5,00-10,00 folds compared to parent molecules. The objective of this review article is to discuss reports on various LHRH analogs with special emphasis on their prospective application in the medical field. The article also focuses on the attributes that must be taken into account while designing a LHRH therapeutics with special account to the biochemistry and applications of these conjugates. The record on various cytotoxic analogs of LHRH are also discussed. It is anticipated that the knowledge of therapeutic and toxicological aspects of LHRH compounds will facilitate the development of a more systematic approach to the targeted delivery of cytotoxic agents using peptides.

The Warburg effect and glucose-derived cancer theranostics.

Tumor cells are known for their propensity to proliferate uncontrollably and generate multitudes of metastatic masses at the advanced stages of cancer. During this progression, tumor cells switch their energy source from mitochondrial oxidative phosphorylation to a glucose-dependent glycolytic pathway, despite the availability of oxygen. Consequently, tumor cells increase their metabolic rates as well as glucose uptake to maintain their proliferation. This atypical metabolic phenomenon is known as the Warburg effect, which has been recognized as a hallmark of cancer and serves as a promising target for diagnosis and therapy of cancer. In this review, we summarize the current advances toward the development of glucose-derived therapeutic and diagnostic agents (theranostics) of cancer.

Application of Chitosan and its Derivatives in Nanocarrier Based Pulmonary Drug Delivery Systems.

BACKGROUND: The respiratory tract as a non-invasive route of drug administration is gaining increasing attention in the present time on achieving both local and the systemic therapeutic effects. Success in achieving pulmonary delivery, requires overcoming barriers including mucociliary clearance and uptake by macrophages. An effective drug delivery system delivers the therapeutically active moieties at the right time and rate to target sites. A major limitation associated with most of the currently available conventional and controlled release drug delivery devices is that not all the drug candidates are well absorbed uniformly locally or systemically. METHODS: We searched and reviewed the literature focusing on chitosan and chitosan derivative based nanocarrier systems used in pulmonary drug delivery. We focused on the applications of chitosan in the development of nanoparticles for this purpose. RESULTS: Chitosan, a natural linear bio-polyaminosaccharide is central in the development of novel drug delivery systems (NDDS) including nanoparticles for use in the treatment of various respiratory diseases. It achieves this through its unique properties of biodegradability, biocompatibility, mucoadhesivity and its ability to enhance macromolecule permeation across membranes. It also achieves sustained and targeted effects, primary requirements for an effective pulmonary drug delivery system. This review highlights the applications and importance of chitosan with special emphasis on nanotechnology, employed in the management of respiratory diseases such as asthma, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis. CONCLUSION: This review will be of interest to both the biological and formulation scientists as it provides a summary on the utility of chitosan in pulmonary drug delivery systems. At present, there are no patented chitosan based controlled release products available for pulmonary drug delivery and so this area has enormous potential in the field of respiratory science.

Surface Engineered Dendrimers in siRNA Delivery and Gene Silencing.

BACKGROUND: Therapeutic efficacy of dreadful diseases like cancer, HIV (Human Immunodeficiency Virus) can be enhanced by delivering molecules which regulate function at gene level rather than at receptor level. Silencing RNA is one such approach recently used to silence target gene expressed diseases; and thereby reduce target protein levels. Many of the non-viral vectors are proved to act as carriers for silencing RNA. Dendrimers being one of them have less size, low poly dispersibility index, water solubility, multivalence, and easy surface modification. Many such surface modifications have been carried out to improve the delivery potential of small interfering RNA (siRNA) modified dendrimers compared to simple plain dendrimers. METHODS: Dendrimer was taken as a core whose surface was modified with fluorine, amino acids, phosphate, lipids, folate, specific antibody or RGD (Arg-Gly-Asp). The purpose of these modifications was to increase the therapeutic siRNA efficiency, lower the toxicity and improve the targeting potential of dendrimers. RESULTS: Fluorinated dendrimers have highest electronegativity and highest siRNA loading capacity. Amino acid functionalized dendrimers are made up of endogenous amino acids which improve biocompatibility of dendrimer and endosomal escape. Carbosilane dendrimers increase the gene transfection ability of tissues to be treated. Phosphate dendrimers having hydrophobic backbone and hydrophilic surface increase the permeability towards targeted tissue. Lipid based dendrimer causes endosomal escape and improves the permeability of dendrimers. Targeting of specific tissues is achieved by coupling dendrimer with folate, RGD and specific antibody, thereby reducing off target effect. CONCLUSION: Thus, surface modified dendrimers render a complete pack which offers increased siRNA loading, increased transfection and permeability, efficient targeting, endosomal escape and protecting siRNA from degradation by RNase and other such enzymes. The objective of this manuscript is to provide different approaches currently available for surface modifications of dendrimers and their overall effect on transfection ability of siRNA to target tissues.

Whether a novel drug delivery system can overcome the problem of biofilms in respiratory diseases?

Biofilm comprises a community of microorganisms which form on medical devices and can lead to various threatening infections. It is a major concern in various respiratory diseases like cystic fibrosis, chronic obstructive pulmonary disease, etc. The treatment strategies for such infections are difficult due to the resistance of the microflora existing in the biofilms against various antimicrobial agents, thus posing threats to the patient population. The present era witnesses the beginning of research to understand the biofilm physiology and the associated microfloral diversity by applying -omics approaches. There is very limited information about how the deposition of biofilm on the respiratory devices and lung itself affects the drug delivered, the delivery system, and other implications. The present mini review summarizes the basic introduction to the biofilms and its avoidance using various drug delivery systems with special emphasis on the respiratory diseases. Understanding the approaches, principles, and modes of drug delivery involved in preventing biofilm deposition will be of interest to both biological and formulation scientists, thereby opening avenues to explore the new vistas in biofilm research for identifying better treatments for pulmonary infectious diseases.

Glycyrrhizin Conjugated Dendrimer and Multi-Walled Carbon Nanotubes for Liver Specific Delivery of Doxorubicin.

The purpose of the present investigation was to investigate the drug targeting potential of glycyrrhizin (GL) conjugated dendrimers (GL-PPI) and multi walled carbon nanotubes (GL-MWCNTs) towards liver targeting of a model anti-cancer agent, doxorubicin (DOX). The synthesis was confirmed by FTIR, 1H-NMR and morphology analysis. Higher DOX loading was observed in case of GL-PPI-DOX and GL-MWCNT-DOX (43.02 ± 0.64% and 87.26 0.57%, respectively) than parent nanocarriers. GL attachment considerably reduced the haemolytic toxicity of DOX by 12.38 ± 1.05 and 7.30 ± 0.63% by GL-PPI-DOX and GL-MWCNT-DOX, respectively. MTT cytotoxicity studies, flow cytometry and cell morphology assessment was done in HepG2 cell. The IC50 of DOX was reduced from 4.19±0.05 µM to 2.0±0.01 and 2.7±0.03 µM, respectively by GL-PPI-DOX and GL-MWCNT-DOX, respectively. Flow cytometry and phase contrast microscopy confirmed GL conjugated formulations to be significantly dragging higher cancer cell number of cells in early apoptosis as well as in early apoptotic phase.

Generation dependent safety and efficacy of folic acid conjugated dendrimer based anticancer drug formulations.

PURPOSE: Folate conjugated poly(propyleneimine) (PPI) dendrimer (FPPI) mediated anticancer therapy is being extensively discovered throughout the world. The present investigation was aimed at exploring the targeting potential of Melphalan loaded FPPI of different generations (MP-FPPI) for effective management of cancer. METHODS: The MP-FPPI formulations were compared for drug entrapment efficiency, in vitro release profile, toxicology, folate receptor blockage assay, cell uptake assay, stability studies, and in vivo studies. RESULTS: Upon increasing the dendrimer generation from fourth to fifth, the drug delivery parameters improved negligibly except the toxicological profile that improved exponentially. MTT assay in case of MCF-7 cells depicted the IC 50 values of 8 ± 0.15, 0.9 ± 0.02, 0.2 ± 0.01 and 10 ± 0.17 µM, respectively in case of MP-FPPI3, MP-FPPI4, MP-FPPI5, and free Melphalan suggesting folate based targeting to be the efficacious approach to kill cancer cells. The median survival time for tumor bearing mice treated with MP-FPPI3, MP-FPPI4, MP-FPPI5 and free drug was found to be 23, 59, 62 and 26 days, respectively. CONCLUSIONS: The study concludes fourth generation PPI dendrimer to be superior carrier for folate based tumor targeting compared to third and fifth generation based formulations. This work is expected to provide a significant clue in the selection of "dendrimer generation" for folate mediated cancer targeting therapy.

Dendrimer-stabilized smart-nanoparticle (DSSN) platform for targeted delivery of hydrophobic antitumor therapeutics.

PURPOSE: To formulate dendrimer-stabilized smart-nanoparticle (DSSN; pD-ANP-f) for the targeted delivery of the highly hydrophobic anticancer drug, Paclitaxel (PTXL). METHOD: The developed nanoformulations were evaluated for particle size, surface-charge, loading efficiency, particle density, in-vitro drug release, SEM/TEM, cytotoxicity assay, fluorescence uptake, HPLC quantitative cell uptake assay, flow cytometry, tubulin polymerization, and stability assessments. RESULTS: The developed pD-ANP-f nanoformulation (135.17 ± 7.39 nm; -2.05 ± 0.37 mV and 80.11 ± 4.39% entrapment) exhibited a pH-dependent drug release; remained stable in physiological pH, while rapid releasing PTXL under tumorous environment (pH 5.5). The cytotoxicity assay performed in cervical, breast, blood, and liver cancer cell lines showed pD-ANP-f to be strongly suppressing the growth of cancer cells. We investigated the fluorescence based intracellular trafficking and HPLC based cellular uptake of nanoformulated drug and the result indicates higher cellular uptake of pD-ANP-f compared to other formulations. pD-ANP-f prominently induced apoptosis (73.11 ± 3.84%) and higher polymerization of tubulins (59.73 ± 6.22%). DSSN nanoformulation was found to be extremely biocompatible (<1% hemolytic) compared to naked PTXL (19.22 ± 1.01%) as well as PTXL-dendrimer nanocomplex (8.29 ± 0.71%). CONCLUSION: DSSN strategy is a novel and promising platform for biomedical applications that can be effectively engaged for the delivery of drug/gene/siRNA targeting.