Nano-based Drug Delivery Systems Research Articles

Exploring Nanocarriers for Boosting Entacapone Bioavailability: A Journey through System Characterization and Assessment of Toxicity and Pharmacological and 2D Permeability Paybacks.

Catechol-O-methyltransferase inhibitors (iCOMT), such as entacapone, have been successfully employed to treat tremor-related symptoms of Parkinson's disease. However, iCOMT has been associated with a short half-life and poor oral bioavailability. Nanobased drug delivery systems have often been used to overcome this type of setbacks. Therefore, entacapone was encapsulated in PEGylated poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) via a nanoprecipitation process, as well as in PEGylated nanostructured lipid carriers (NLCs) using a solvent emulsification/evaporation method. Both nanoformulations presented sub-200 nm populations, with zeta-potential (ZP) values close to -30 mV, and showed stability at different pHs, while maintaining their physicochemical properties mostly intact, presenting only a change in their superficial charge (ZP values), indicating their interaction. Both nanoformulations presented interaction with mucins, which anticipates good permeation and bioavailability for oral and topical administration. No cytotoxic effects were observed for lyophilized PLGA NPs encapsulating entacapone, in which 2-hydroxypropyl-ß-cyclodextrin (HPβCD) was used as a cryoprotectant at 3% concentration (HP-PLGA@Ent), in human hepatocellular carcinoma (HepG2), human neuroblastoma (SH-SY5Y), or human epithelial colorectal adenocarcinoma (Caco-2) cell lines. Conversely, NLCs encapsulating entacapone (W-NLCs@Ent) presented cytotoxic effects on the HepG2 cell line, likely due to intracellular lipid accumulation or storage. Both nanoformulations maintained a COMT inhibition effect in HepG2 cells, using 3-BTD as the COMT probe. An increase of entacapone permeability in both monolayer and coculture models (Caco-2 and Caco-2/HT29-MTX, respectively) was observed for the developed nanoformulations. Overall, this work shows that encapsulated entacapone in different nanocarriers could be a stimulating alternative to solve entacapone setbacks, since they improve its physicochemical properties and permeability while still maintaining the COMT inhibitory activity.

α-Mangostin-phytosomes as a plausible nano-vesicular approach for enhancing cytotoxic activity on SKOV-3 ovarian cancer cells

Backgroundα-Mangostin is a major xanthone in Garcinia mangostana L. (Clusiaceae) pericarps. It has promising anti-proliferative potential in different cancer cells; however, it has poor oral bioavailability. Phytosomes are used as a novel nano-based drug delivery system. The aim of this research was to enhance the anti-proliferative potency of α-mangostin by formulating it as α-mangostin-phytosome (α-M-PTMs) and assessing its impact on SKOV-3 ovarian cancer cells in comparison to pure α-mangostin.ResultsThe size and entrapment efficiency of the proposed formulation were optimized using Box–Behnken statistics. The optimized formula was characterized using transmission electron microscope. The binding of α-mangostin to phospholipids was confirmed using Fourier-transform infrared (FTIR) spectroscopy. The optimized α-mangostin-phytosomes formula exhibited enhanced anti-proliferative activity with reference to raw α-mangostin. This was further substantiated by assessing the cell cycle phases that indicated an accumulation of SKOV-3 cells in the sub-G1 phase. Annexin-V staining revealed enhanced apoptotic activity in α-mangostin-phytosome-treated cells. This was associated with upregulation of CASP3 (Caspase-3), BAX (BCL2 Associated X, Apoptosis Regulator) and TP53 as well as down-regulation of BCL2 mRNA (B-Cell Leukemia/Lymphoma 2). Moreover, our data indicated enhanced ROS (Reactive oxygen species) production, cytochrome-C release, and disturbed MMP (mitochondrial membrane potential).ConclusionEncapsulation of α-mangostin in a phytosome nano-formula enhances its anti-proliferative effects in SKOV-3 cells via, at least in part, inducing mitochondrial apoptotic cell death.

Enhancement of Temozolomide Stability and Anticancer Efficacy by Loading in Monopalmitolein-Based Cubic Phase Nanoparticles.

Temozolomide (TMZ) is a prodrug possessing a wide spectrum of anticancer activities. TMZ is pharmacologically inactive, but at a physiological pH, it is quickly converted to an active metabolite, 5-aminoimidazole-4-carboxamide, and a methyldiazonium cation. Due to its chemical nature, TMZ presents some capability of crossing the blood-brain barrier and therefore is used as a first-line agent in the treatment of gliomas. Here, we aimed to improve the anticancer effectiveness of TMZ by loading it into cubosomes, which are lipid nanoparticles recognized as efficient nano-based drug delivery systems. TMZ was incorporated into the monoolein (MO)- and monopalmitolein (MP)-derived cubic phases to improve its stability and half-life. It was considered that the drug release rate may vary between the MO and MP cubosomes, as the water channels of MP phases are larger than those of MO cubosomes. Therefore, we expected that due to the MPs' ability to entrap more drug molecules inside the mesophase, the concentration of TMZ available to cancer cells would be enhanced. This assumption was supported by biological analyses using the A-172 and drug-resistant T98G glioma-derived cell lines. The strongest reduction in viability was observed for A-172 cells treated with TMZ-loaded MP nanoparticles. Importantly, the TMZ-loaded MPs also caused a significant anticancer effect in the drug-resistant T98G glioma-derived cells. Both MO and MP empty cubic phases did not affect the survival of the tested cells. Concluding, TMZ-loaded cubosomes present strong anticancer properties. Encapsulating the drug within the lipid nanostructure helps to protect the drug from degradation and allows for greater accumulation of TMZ at the tumor site. Together with chemical-based features of mesophases related to increased cargo size and kinetic properties, we imply that MPs may be considered as a highly efficient nano-based drug delivery system to treat poorly curable tumors including gliomas.

The electro-responsive nanoliposome as an on-demand drug delivery platform for epilepsy treatment

Nano-based drug delivery systems are regarded as a promising tool for efficient epilepsy treatment and seizure medication with the least general side effects and socioeconomic challenges. In the current study, we have designed a smart nanoscale drug delivery platform and applied it in the kindling model of epilepsy that is triggered rapidly by epileptic discharges and releases anticonvulsant drugs in situ, such as carbamazepine (CBZ). The CBZ-loaded electroactive ferrocene nanoliposomes had an average diameter of 100.6 nm, a surface charge of −7.08 mV, and high drug encapsulation efficiency (85.4 %). A significant increase in liposome size was observed in response to direct current (50–500 μA) application. This liposome-based drug delivery system can release CBZ at a fast rate in response to both direct current and pulsatile electrical stimulation in vitro. The CBZ-liposome can release the anticonvulsant drug upon epileptiform activity in the kindled rat model and can decline electrographic and behavioral seizure activity in response to electrical stimulation of the hippocampus with an initially subconvulsive current. With satisfactory biosafety results, this “smart” nanocarrier has promising potential as an effective and safe drug delivery system to improve the therapeutic index of antiepileptic drugs.

Folate receptor-targeted indomethacin-loaded gold nanoparticles enhance drug chemotherapeutic efficacy in glioblastoma cells and spheroids

Glioblastoma is a highly malignant brain cancer with a poor survival rate. Increasing evidence demonstrates the anticancer activity, including anti-glioma activity, of indomethacin (IND), a non-steroidal anti-inflammatory drug. However, due to the IND's poor aqueous solubility, nano-based drug delivery systems, especially gold nanoparticles (AuNPs), are great tools for increasing solubility and therapeutic efficacy. Herein, glutathione (GSH)-coated folic acid (FA)-modified AuNPs were used for the first time to generate IND-loaded AuNPs (55 nm), which were successfully synthesized according to DLS, TEM, FTIR, NMR, and TGA results. IND/AuNPs were found to have spherical morphology, nanoscale particle size, narrow size distribution, and good stability. Fluorescence and confocal imaging demonstrated that the nanoparticles penetrated folate receptor (FR)+ U-87MG human glioblastoma monolayer and sphere-forming cells. Remarkably, short-term exposure (4h) to IND/AuNPs significantly increased IND cytotoxicity in U-87MG cells after post-44h and -68h (>35- and >120-fold, respectively). Even against prolonged exposure of cells to IND for 24h, 48h, and 72h, IND/AuNP treatment revealed a marked result: glioma proliferation slowed by 7.38-fold, 6.8-fold, and 17-fold, respectively. No significant effect was observed on the FR− cell lines. The increased antitumoral activity was accompanied by efficient increased apoptosis in glioblastoma cells due to the IND/AuNP treatments. Moreover, compared to free-drug and control groups, IND/AuNP treatments markedly reduced glioblastoma growth in 3D spheroids (in vitro system that mimics in vivo tumors). Therefore, these findings suggest that the new spherical IND/Au-GSH-FA NP conjugate has the potential to be a beneficial therapeutic agent in glioblastoma therapy by targeting FRs.

Research advances on signaling pathways regulating the polarization of tumor-associated macrophages in lung cancer microenvironment.

Lung cancer (LC) is one of the most common cancer worldwide. Tumor-associated macrophages (TAMs) are important component of the tumor microenvironment (TME) and are closely related to the stages of tumor occurrence, development, and metastasis. Macrophages are plastic and can differentiate into different phenotypes and functions under the influence of different signaling pathways in TME. The classically activated (M1-like) and alternatively activated (M2-like) represent the two polarization states of macrophages. M1 macrophages exhibit anti-tumor functions, while M2 macrophages are considered to support tumor cell survival and metastasis. Macrophage polarization involves complex signaling pathways, and blocking or regulating these signaling pathways to enhance macrophages' anti-tumor effects has become a research hotspot in recent years. At the same time, there have been new discoveries regarding the modulation of TAMs towards an anti-tumor phenotype by synthetic and natural drug components. Nanotechnology can better achieve combination therapy and targeted delivery of drugs, maximizing the efficacy of the drugs while minimizing side effects. Up to now, nanomedicines targeting the delivery of various active substances for reprogramming TAMs have made significant progress. In this review, we primarily provided a comprehensive overview of the signaling crosstalk between TAMs and various cells in the LC microenvironment. Additionally, the latest advancements in novel drugs and nano-based drug delivery systems (NDDSs) that target macrophages were also reviewed. Finally, we discussed the prospects of macrophages as therapeutic targets and the barriers to clinical translation.

The Use of Nano-based Drug Delivery Systems for Neurodegenerative Disorders

ABSTRACT Blood–brain interfaces surrounding the central nervous system (CNS) present problems for targeted drug delivery, which limits the bioavailability of therapies for the diagnosis and treatment of neurological illnesses such as Alzheimer’s diseases and Parkinson’s diseases (AD/PD). Over the past 10 years, research has concentrated on creating novel approaches to get around these restrictions and effectively transport medications to the CNS. The protective barriers surrounding the CNS can be penetrated by nanoparticles (NPs), which have the ability to encapsulate medicines with prolonged drug release patterns and customizable physiochemical properties. To find out more about drug delivery systems, blood–brain barrier, NPs, neurodegenerative illnesses, AD and PD, and their treatment applications, a ScienceDirect, PubMed, and Google Scholar search was done. After analysis using the keywords/phrases, relevant articles were determined to be completed. Because nanotechnology is a potent substitute for traditional drug delivery systems, it thus offers new hope for the treatment of AD and PD for example. The possible use of techniques based on NPs in neurodegenerative disorders and their therapeutic implications are covered briefly in this work.

Nano-based drug delivery systems for active ingredients from traditional Chinese medicine: Harnessing the power of nanotechnology.

Introduction: Traditional Chinese medicine (TCM) is gaining worldwide popularity as a complementary and alternative medicine. The isolation and characterization of active ingredients from TCM has become optional strategies for drug development. In order to overcome the inherent limitations of these natural products such as poor water solubility and low bioavailability, the combination of nanotechnology with TCM has been explored. Taking advantage of the benefits offered by the nanoscale, various drug delivery systems have been designed to enhance the efficacy of TCM in the treatment and prevention of diseases. Methods: The manuscript aims to present years of research dedicated to the application of nanotechnology in the field of TCM. Results: The manuscript discusses the formulation, characteristics and therapeutic effects of nano-TCM. Additionally, the formation of carrier-free nanomedicines through self-assembly between active ingredients of TCM is summarized. Finally, the paper discusses the safety behind the application of nano-TCM and proposes potential research directions. Discussion: Despite some achievements, the safety of nano-TCM still need special attention. Furthermore, exploring the substance basis of TCM formulas from the perspective of nanotechnology may provide direction for elucidating the scientific intension of TCM formulas.

Nanomedicines: Nano based Drug Delivery Systems Challenges and Future of nanomedicines

Over the past ten years, the research and delivery of drugs has emerged as a rapidly expanding, highly capital-intensive, and demanding industry. This procedure is costly and time-consuming, and it has to deal with issues with rapid excretion, degradability, toxicity, low efficacy, biocompatibility, and low bioavailability. Nanomaterial are superior to conventional drug because they have remarkable qualities such as a high invasion rate, regulated, targeted, and gradual drug release, as well as easy receptor accessibility. Despite all of its importance, one of the main issues with different nanoparticles utilized as medication delivery systems is their toxicity. This review discusses the issue surrounding conventional drugs, the importance of nanomedicines in medication administration, and their potential for toxicity and also their future aspect that helps to improve health.

A Review of Recent Developments in Biopolymer Nano-Based Drug Delivery Systems with Antioxidative Properties: Insights into the Last Five Years.

In recent years, biopolymer-based nano-drug delivery systems with antioxidative properties have gained significant attention in the field of pharmaceutical research. These systems offer promising strategies for targeted and controlled drug delivery while also providing antioxidant effects that can mitigate oxidative stress-related diseases. Generally, the healthcare landscape is constantly evolving, necessitating the continual development of innovative therapeutic approaches and drug delivery systems (DDSs). DDSs play a pivotal role in enhancing treatment efficacy, minimizing adverse effects, and optimizing patient compliance. Among these, nanotechnology-driven delivery approaches have garnered significant attention due to their unique properties, such as improved solubility, controlled release, and targeted delivery. Nanomaterials, including nanoparticles, nanocapsules, nanotubes, etc., offer versatile platforms for drug delivery and tissue engineering applications. Additionally, biopolymer-based DDSs hold immense promise, leveraging natural or synthetic biopolymers to encapsulate drugs and enable targeted and controlled release. These systems offer numerous advantages, including biocompatibility, biodegradability, and low immunogenicity. The utilization of polysaccharides, polynucleotides, proteins, and polyesters as biopolymer matrices further enhances the versatility and applicability of DDSs. Moreover, substances with antioxidative properties have emerged as key players in combating oxidative stress-related diseases, offering protection against cellular damage and chronic illnesses. The development of biopolymer-based nanoformulations with antioxidative properties represents a burgeoning research area, with a substantial increase in publications in recent years. This review provides a comprehensive overview of the recent developments within this area over the past five years. It discusses various biopolymer materials, fabrication techniques, stabilizers, factors influencing degradation, and drug release. Additionally, it highlights emerging trends, challenges, and prospects in this rapidly evolving field.

Chitosan mediated smart photodynamic therapy based novel drug delivery systems- a futuristic view

In order to improve the pharmacological and therapeutic properties of drugs, researchers have attempted numerous novel approaches, such as stimuli-responsive systems, and targeted drug delivery systems. These systems can be attempted by nano-based drug delivery systems involving biocompatible polymers. One among which is chitosan, a linear polysaccharide, a promising potential polymer that gained interest in delivering challenging drugs. Chitosan can encapsulate and release the drugs in a controlled/sustained manner. Chitosan can be used to develop a variety of drug delivery carriers, including films, gels, nanoparticles, nanodispersions, nanomicelles, and patches. In this regimen, minimally invasive photodynamic therapy has recently gained much interest in treating vascular diseases, including cancer, ocular diseases, microbial infections, skin disorders, etc. Photodynamic therapy utilizes light excited at a specific wavelength, eliciting singlet oxygen production. Self-lighting photodynamic therapy and combination-based photodynamic therapy also offer synergistic effects. Photodynamic therapy is more selective and specific, which may offer treatment for deep-seated diseased tissues compared to conventional therapeutic modalities. Light-activated novel drug delivery formulations have been reported using various biocompatible polymers, including chitosan. Chitosan offers its effectiveness as mucoadhesiveness, tissue penetrability, antioxidant, antimicrobial properties, supports in singlet oxygen generation, and shown its benefits in photodynamic therapy. Therefore, this review presents numerous applications of chitosan-based light-activated drug delivery systems with particular emphasis on their patents and clinical trials. The literature has been collected and compiled using various search resources such as Science Direct, J-Gate, Google Scholar, PubMed, and research data.

Nanoparticle-Mediated Synergistic Chemoimmunotherapy for Cancer Treatment.

Until now, there has been a lack of effective strategies for cancer treatment. Immunotherapy has high potential in treating several cancers but its efficacy is limited as a monotherapy. Chemoimmunotherapy (CIT) holds promise to be widely used in cancer treatment. Therefore, identifying their involvement and potential synergy in CIT approaches is decisive. Nano-based drug delivery systems (NDDSs) are ideal delivery systems because they can simultaneously target immune cells and cancer cells, promoting drug accumulation, and reducing the toxicity of the drug. In this review, we first introduce five current immunotherapies, including immune checkpoint blocking (ICB), adoptive cell transfer therapy (ACT), cancer vaccines, oncolytic virus therapy (OVT) and cytokine therapy. Subsequently, the immunomodulatory effects of chemotherapy by inducing immunogenic cell death (ICD), promoting tumor killer cell infiltration, down-regulating immunosuppressive cells, and inhibiting immune checkpoints have been described. Finally, the NDDSs-mediated collaborative drug delivery systems have been introduced in detail, and the development of NDDSs-mediated CIT nanoparticles has been prospected.

A holistic review of recent advances in nano-based drug delivery systems for the treatment of triple-negative breast cancer (TNBC)

A holistic review of recent advances in nano-based drug delivery systems for the treatment of triple-negative breast cancer (TNBC)

Self-assembled nanoparticle-mediated cascade chemotherapy and chemodynamic therapy for enhanced tumor therapy

Chemodynamic therapy (CDT) is a non-invasive treatment strategy that aims to combat tumor growth by efficiently generating reactive oxygen species (ROS). However, the effectiveness of CDT can be limited by factors such as the availability of endogenous hydrogen peroxide (H2O2). Here, we established an intelligent nano-based drug delivery system responsive to the tumor microenvironment by self-assembling Cu2+, cisplatin, and L-histidine to form nanoparticles (Pt/CuH NPs), which can achieve the therapeutic effect of specific tumor killing by cascading chemotherapy with CDT. The Pt/CuH NPs are triggered by the acidic conditions and high glutathione (GSH) levels present in the tumor microenvironment, leading to the release of cisplatin and Cu2+. Cisplatin facilitates the production of H2O2 through a two-step enzymatic reaction, subsequently triggering ROS cascade that is amplified by CDT. Concurrently, Cu2+ consumes GSH and is reduced to Cu+, which reacts with H2O2 in an efficient Fenton-like reaction, amplifying oxidative stress and ultimately enhancing the anti-tumor therapeutic efficacy. Pt/CuH NPs demonstrated a significant cytotoxic effect on tumor cells in vitro. In vivo studies in mice indicated minimal toxic side effects at the tested dosages. The Pt/CuH NPs effectively combine chemotherapy and CDT strategies, showcasing the potential of a chemotherapy-cascading CDT approach for anti-tumor treatment.

Polydopamine-Mediated Metal-Organic Frameworks Modification for Improved Biocompatibility.

Engineered nanomaterials are promising in biomedical application. However, insufficient understanding of their biocompatibility at the cellular and organic levels prevents their widely biomedical applications. Metal-organic frameworks (MOFs) have attracted increasing attention in recent years. In this work, zeolitic imidazolate framework-8 (ZIF-8) and polydopamine (PDA)-modified ZIF-8 are chosen as model nanomaterials due to its emergent role in nanomedicine. In vitro, the results demonstrate that the PDA coating greatly alleviates the cytotoxicity of ZIF-8 to RAW264.7, LO2, and HST6, which represent three different cell types in liver organs. Mechanistically, ZIF-8 entering into the cells can greatly induce the reactive oxygen species generation, which subsequently induces cell cycle delay and autophagy, ultimately leads to enhanced cytotoxicity. Further, human umbilical vein endothelial cells model and zebrafish embryos assay also confirm that PDA can compromise the ZIF-8 toxicity significantly. This study reveals that PDA-coated MOFs nanomaterials show great potential in nano-based drug delivery systems .

Cationic anticancer peptide L-K6-modified and doxorubicin-loaded mesoporous silica nanoparticles reverse multidrug resistance of breast cancer

Multidrug resistance (MDR) is the major challenge for chemotherapy of cancer and makes the treatment benefits unsustainable. To overcome this issue, nanotechnology has been introduced and various nanocarriers have been constructed to reverse MDR in drug resistant cancer cells. Here, mesoporous silica nanoparticle (MSN-COOH) were modified with cationic anticancer peptide L-K6 (MSN@L-K6), and further loaded with doxorubicin (DOX) to construct an anticancer nano-system, MSN@L-K6@DOX. Our results showed that MSN@L-K6@DOX released DOX in pH-sensitive manner, which enable to be highly efficient in delivering drugs to tumors, counterbalancing the MDR. In addition, MSN@L-K6@DOX treatment decreased the expression level of P-glycoprotein in MCF-7/ADR cells, enhanced the intracellular accumulation of DOX, and thereafter reversed the MDR of MCF-7/ADR cells to DOX. Moreover, the MDR reversal activity of MSN@L-K6@DOX was further confirmed in xenograft mouse model, as evidenced by the decreased tumor volume and weight. These results indicate the MDR reversal activity of MSN@L-K6@DOX and may provide a novel strategy for the development of nano-based drug delivery system to overcome cancer MDR.

Pathophysiological aspects of transferrin-A potential nano-based drug delivery signaling molecule in therapeutic target for varied diseases.

Transferrin (Tf), widely known for its role as an iron-binding protein, exemplifies multitasking in biological processes. The role of Tf in iron metabolism involves both the uptake of iron from Tf by various cells, as well as the endocytosis mediated by the complex of Tf and the transferrin receptor (TfR). The direct conjugation of the therapeutic compound and immunotoxin studies using Tf peptide or anti-Tf receptor antibodies as targeting moieties aims to prolong drug circulation time and augment efficient cellular drug uptake, diminish systemic toxicity, traverse the blood-brain barrier, restrict systemic exposure, overcome multidrug resistance, and enhance therapeutic efficacy with disease specificity. This review primarily discusses the various biological actions of Tf, as well as the development of Tf-targeted nano-based drug delivery systems. The goal is to establish the use of Tf as a disease-targeting component, accentuating the potential therapeutic applications of this protein.

Benefits and Pitfalls of a Glycosylation Inhibitor Tunicamycin in the Therapeutic Implication of Cancers.

The aberrant glycosylation is a hallmark of cancer progression and chemoresistance. It is also an immune therapeutic target for various cancers. Tunicamycin (TM) is one of the potent nucleoside antibiotics and an inhibitor of aberrant glycosylation in various cancer cells, including breast cancer, gastric cancer, and pancreatic cancer, parallel with the inhibition of cancer cell growth and progression of tumors. Like chemotherapies such as doxorubicin (DOX), 5'fluorouracil, etoposide, and cisplatin, TM induces the unfolded protein response (UPR) by blocking aberrant glycosylation. Consequently, stress is induced in the endoplasmic reticulum (ER) that promotes apoptosis. TM can thus be considered a potent antitumor drug in various cancers and may promote chemosensitivity. However, its lack of cell-type-specific cytotoxicity impedes its anticancer efficacy. In this review, we focus on recent advances in our understanding of the benefits and pitfalls of TM therapies in various cancers, including breast, colon, and pancreatic cancers, and discuss the mechanisms identified by which TM functions. Finally, we discuss the potential use of nano-based drug delivery systems to overcome non-specific toxicity and enhance the therapeutic efficacy of TM as a targeted therapy.

Key processes in tumor metastasis and therapeutic strategies with nanocarriers: a review.

Cancer metastasis is the leading cause of cancer-related death. Metastasis occurs at all stages of tumor development, with unexplored changes occurring at the primary site and distant colonization sites. The growing understanding of the metastatic process of tumor cells has contributed to the emergence of better treatment options and strategies. This review summarizes a range of features related to tumor cell metastasis and nanobased drug delivery systems for inhibiting tumor metastasis. The mechanisms of tumor metastasis in the ideal order of metastatic progression were summarized. We focus on the prominent role of nanocarriers in the treatment of tumor metastasis, summarizing the latest applications of nanocarriers in combination with drugs to target important components and processes of tumor metastasis and providing ideas for more effective nanodrug delivery systems.

Recent Development and Future Aspects: Nano-Based Drug Delivery System in Cancer Therapy

Recent Development and Future Aspects: Nano-Based Drug Delivery System in Cancer Therapy