Nanocarrier-based Drug Delivery Systems Research Articles

Nanotechnology and Nanocarrier-Based Drug Delivery as the Potential Therapeutic Strategy for Glioblastoma Multiforme: An Update.

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor with poor prognosis. The heterogeneous and aggressive nature of GBMs increases the difficulty of current standard treatment. The presence of GBM stem cells and the blood brain barrier (BBB) further contribute to the most important compromise of chemotherapy and radiation therapy. Current suggestions to optimize GBM patients' outcomes favor controlled targeted delivery of chemotherapeutic agents to GBM cells through the BBB using nanoparticles and monoclonal antibodies. Nanotechnology and nanocarrier-based drug delivery have recently gained attention due to the characteristics of biosafety, sustained drug release, increased solubility, and enhanced drug bioactivity and BBB penetrability. In this review, we focused on recently developed nanoparticles and emerging strategies using nanocarriers for the treatment of GBMs. Current studies using nanoparticles or nanocarrier-based drug delivery system for treatment of GBMs in clinical trials, as well as the advantages and limitations, were also reviewed.

Targeting to Brain Tumor: Nanocarrier-Based Drug Delivery Platforms, Opportunities, and Challenges.

Cancer is a class of disorder characterized by anomalous growth of cells escalating in an uncontrolled way. Among all the cancers, treatment of cancerous brain tumors has been a tough challenge for the research scientists. Moreover, the absence of early-stage symptoms delays its diagnosis, consequently worsening its severity. Conventional treatments such as surgery, radiation, and chemotherapy are still linked with several limitations. The therapeutic effect of most of the anticancer drugs is highly restricted by their inability to pass the blood–brain barrier, low solubility, limited therapeutic window, and so on. Alarming incidences of brain cases associated with low survival rate across the globe coupled with the inefficiency of current treatment strategies have forced the formulation scientists to investigate nanotechnology-based advanced therapeutic approaches to tackle the disease. Various nanoplatforms such as polymeric nanoparticles (NPs), nanoliposomes, dendrimers, carbon nanotubes, and magnetic NPs have been reported in the past years to improve the drug administration into brain tumor cells and to minimize their off-target distribution for lesser side effects and better treatment outcomes. The review presents updated information on the nanocarrier-based drug delivery systems reported in the past few years for the treatment of brain tumor along with new advancements in this field. It also throws some light on the recent challenges faced in the practical field for the successful clinical translation of such nanodrug carriers along with a discussion on the future prospects.

Nanocarrier-based Drug Delivery System for Cancer Therapeutics: A Review of the Last Decade

Nanocarrier-based Drug Delivery System for Cancer Therapeutics: A Review of the Last Decade

PH – Responsive colloidal carriers assembled from β-lactoglobulin and Epsilon poly-L-lysine for oral drug delivery

Site specific oral delivery of many biopharmaceutical classification system (BCS) class II and IV drugs is challenging due to their poor solubility, low permeability and degradation in the gastrointestinal tract. Whilst colloidal carriers have been used to improve the bioavailability of such drugs, most nanocarriers based drug delivery systems suffer from multiple disadvantages, including low encapsulation efficiency (liposomes, polymeric nanoparticles), complex synthesis methods (silica, silicon-based materials) and poorly understood biodegradability (inorganic nanoparticles). Herein, a novel pH responsive nanocolloids were self-assembled using natural compounds such as bovine β-lactoglobulin (BLG) and succinylated β-lactoglobulin (succ. BLG) cross-linked with epsilon poly l-lysine (BCEP and BCP), and found to possess high loading capacity, high aqueous solubility and site-specific oral delivery of a poorly soluble nutraceutical (curcumin), improving its physicochemical properties and biological activity in-vitro and ex-vivo. Our optimized synthesis formed colloids of around 200 nm which were capable of encapsulating curcumin with ~100% encapsulation efficiency and ~10% w/w drug loading. By forming nanocomplexes of curcumin with BLG and succ. BLG, the aqueous solubility of curcumin was markedly increased by ~160-fold and ~86-fold, respectively. Encapsulation with BLG increased the solubility, whereas succ. BLG prevent release of encapsulated curcumin when subjected to gastric fluids as it is resistant to breakdown on exposure to pepsin at acidic pH. In conditions mimicking the small intestine, Succ. BLG was more soluble resulting in sustained release of the encapsulated drug at pH 7.4. Additionally, crosslinking succ. BLG with E-PLL significantly enhanced curcumin’s permeability in an in-vitro Caco-2 cell monolayer model compared to curcumin solution (dissolved in 1% DMSO), or non-crosslinked BLG/succ. and BLG. In a mouse-derived intestinal epithelial 3D organoid culture stimulated with IL-1β, BLG-CUR and crosslinked BCEP nanoparticles reduced the production of inflammatory cytokines and chemokines such as Tnfα and Cxcl10 more than curcumin solution or suspension while these nanoparticles were non-toxic to organoids. Overall this work demonstrates the promise of nutraceutical-based hybrid self-assembled colloidal system to protect hydrophobic drugs from harsh gastrointestinal conditions and improve their solubility, dissolution, permeability and biological activity.

Advancing of Cellular Signaling Pathways in Respiratory Diseases Using Nanocarrier Based Drug Delivery Systems.

Cell Signaling pathways form an integral part of our existence that allows the cells to comprehend a stimulus and respond back. Such reactions to external cues from the environment are required and are essential to regulate the normal functioning of our body. Abnormalities in the system arise when there are errors developed in these signals, resulting in a complication or a disease. Presently, respiratory diseases contribute to being the third leading cause of morbidity worldwide. According to the current statistics, over 339 million people are asthmatic, 65 million are suffering from COPD, 2.3 million are lung cancer patients and 10 million are tuberculosis patients. This toll of statistics with chronic respiratory diseases leaves a heavy burden on society and the nation's annual health expenditure. Hence, a better understanding of the processes governing these cellular pathways will enable us to treat and manage these deadly respiratory diseases effectively. Moreover, it is important to comprehend the synergy and interplay of the cellular signaling pathways in respiratory diseases, which will enable us to explore and develop suitable strategies for targeted drug delivery. This review, in particular, focuses on the major respiratory diseases and further provides an in-depth discussion on the various cell signaling pathways that are involved in the pathophysiology of respiratory diseases. Moreover, the review also analyses the defining concepts about advanced nano-drug delivery systems involving various nanocarriers and propose newer prospects to minimize the current challenges faced by researchers and formulation scientists.

Nanocarrier-based Drug Delivery System for Cancer Therapeutics: A Review of the Last Decade.

In recent years, due to the shortcomings of conventional chemotherapy, such as poor bioavailability, low treatment index, and unclear side effects, the focus of cancer research has shifted to new nanocarriers of chemotherapeutic drugs. By using biodegradable materials, nanocarriers generally have the advantages of good biocompatibility, low side effects, targeting, controlled release profile, and improved efficacy. More to the point, nanocarrier based anti-cancer drug delivery systems clearly show the potential to overcome the problems associated with conventional chemotherapy. In order to promote the in-depth research and development in this field, we herein summarized and analyzed various nanocarrier based drug delivery systems for cancer therapy, including the concepts, types, characteristics, and preparation methods. The active and passive targeting mechanisms of cancer therapy were also included, along with a brief introduction of the research progress of nanocarriers used for anti-cancer drug delivery in the past decade.

Recent Nanocarrier Approaches for Targeted Drug Delivery in Cancer Therapy.

Cancer is one of the most serious health concerns in the 21st century whose prevalence is beyond boundaries and can affect any organ of the human body. The conventional chemotherapeutic treatment strategies lack specificity to tumors and are associated with toxic effects on the immune system and other organ systems. In the past decades, there has been continuous progress in the development of smart nanocarrier systems for target-specific delivery of drugs against a variety of tumors, including intracellular gene-specific targeting. These nanocarriers are able to recognize the tumor cells and deliver the therapeutic agent in fixed proportions, causing no or very less harm to healthy cells. Nanosystems have modified physicochemical properties, improved bioavailability, and long retention in blood, which enhances their potency. A huge number of nanocarrier based formulations have been developed and are in clinical trials. Nanocarrier systems include polymeric micelles, liposomes, dendrimers, carbon nanotubes, gold nanoparticles, etc. Recent advancements in nanocarrier systems include mesoporous silica nanoparticles (MSNs), metal organic frameworks, and quantum dots. In the present review, various nanocarrier based drug delivery systems, along with their applications in the management of cancer, have been described with special emphasis on MSNs.

Internalization Mechanisms of Pyridinium Sulfobetaine Polymers Evaluated by Induced Protic Perturbations on Cell Surfaces.

Understanding the interactions of soft nanomatters with cell membranes is particularly important for research into nanocarrier-based drug delivery systems, cell engineering, and subcellular imaging. Most nanoparticles, vesicles, micelles, and polymeric aggregates are internalized into endosomes and, eventually, lysosomes in the cytosol because of energy-dependent endocytic processes. Endocytic uptake substantially limits the access to the cytoplasm where a cargo agent acts. Bypassing the endocytic pathways by direct penetration into plasma membrane barriers would enhance the efficacy of nanomedicines. Some zwitterionic polymer nanoaggregates have been shown to permeate into the cell interior in an energy-independent manner. We have elucidated this phenomenon by observing changes in the biomembrane barrier functions against protons as the smallest indicator and have used these results to further design and develop poly(betaines). In this work, we investigated the translocation mechanisms for a series of zwitterionic poly(methacrylamide) and poly(methacrylate) species bearing a pyridinium propane sulfonate moiety in the monomers. Minor differences in the monomer structures and functional groups were observed to have dramatic effects on the interaction with plasma membranes during translocation. The ability to cross the plasma membrane involves a balance among the betaine dipole-dipole interaction, NH-π interaction, π-π interaction, cation-π interaction, and amide hydrogen bonding. We found that the cell-penetrating polysulfobetaines had limited or no detrimental effect on cell proliferation. Our findings enhance the opportunity to design and synthesize soft nanomatters for cell manipulations by passing across biomembrane partitions.

Dendrimer Conjugation Enhances Tumor Penetration and Efficacy of Doxorubicin in Extracellular Matrix-Expressing 3D Lung Cancer Models.

Doxorubicin (DOX) is a chemotherapeutic agent broadly used in the treatment of a range of solid tumors. In spite of its high potency, as is the case for many other chemotherapeutic drugs, there are many challenges associated with the use of DOX in clinical oncology. This is particularly true for DOX in the treatment of lung cancer, where in vitro potency is shown to be very high, but low lung distribution and off-target toxicity (particularly cardiotoxicity) restrict its use. Nanocarrier-based drug delivery systems (nanoDDS) have been shown to help alter biodistribution and alleviate off-target toxicity associated with DOX. While significant understanding exists regarding the design parameters to achieve those clinical benefits, much less is known regarding the design of nanoDDS capable of enhancing tumor penetration of DOX (and other drugs), which is another major factor leading to DOX's reduced efficacy. The purpose of this study was to design a dendrimer-based nanoDDS capable of enhancing the penetration of DOX as measured in an in vitro 3D lung tumor model and to correlate those results with its efficacy. Spheroids formed with the A549 human lung adenocarcinoma cells/murine fibroblast cell line (NIH/3T3 cell line) are shown to produce the essential components of the extracellular matrix (ECM), which is known as a physical barrier that hinders the transport of DOX. DOX was conjugated to generation 4 succinamic acid-terminated poly(amido-amine) (PAMAM) dendrimers (G4SA) through an enzyme-liable tetrapeptide (G4SA-GFLG-DOX), resulting in a nanoDDS with ∼5.5 DOX, -17 mV surface (ζ) potential, and a 10 nm hydrodynamic diameter (HD). The penetration of DOX to the core of the spheroid in terms of DOX fluorescence was determined to be 3.1-fold greater compared to free DOX, which positively correlated with enhanced efficacy as measured by the Caspase 3/7 assay. This improved penetration happens as the interactions between the G4SA-GFLG-DOX and the highly negatively charged ECM are minimized by shielding the protonatable amine of DOX upon conjugation, and the HD of the conjugate is kept smaller than the estimated mesh size of the ECM. Interestingly, the conjugate provided more specificity for DOX to tumor cells compared to fibroblasts, while free DOX is equally distributed in both tumor and fibroblasts as assessed in the coculture spheroids. Growth inhibition studies show that the released DOX maintains its activity and leads to tumor reduction to the same extent as free DOX. The results obtained here are of relevance for the design of dendrimer-based nanoDDS and for the treatment of solid tumors as they provide critical information regarding desirable surface characteristics and sizes for efficient tumor penetration.

Nanocarrier-Based Therapeutics and Theranostics Drug Delivery Systems for Next Generation of Liver Cancer Nanodrug Modalities.

The development of therapeutics and theranostic nanodrug delivery systems have posed a challenging task for the current researchers due to the requirement of having various nanocarriers and active agents for better therapy, imaging, and controlled release of drugs efficiently in one platform. The conventional liver cancer chemotherapy has many negative effects such as multiple drug resistance (MDR), high clearance rate, severe side effects, unwanted drug distribution to the specific site of liver cancer and low concentration of drug that finally reaches liver cancer cells. Therefore, it is necessary to develop novel strategies and novel nanocarriers that will carry the drug molecules specific to the affected cancerous hepatocytes in an adequate amount and duration within the therapeutic window. Therapeutics and theranostic systems have advantages over conventional chemotherapy due to the high efficacy of drug loading or drug encapsulation efficiency, high cellular uptake, high drug release, and minimum side effects. These nanocarriers possess high drug accumulation in the tumor area while minimizing toxic effects on healthy tissues. This review focuses on the current research on nanocarrier-based therapeutics and theranostic drug delivery systems excluding the negative consequences of nanotechnology in the field of drug delivery systems. However, clinical developments of theranostics nanocarriers for liver cancer are considered outside of the scope of this article. This review discusses only the recent developments of nanocarrier-based drug delivery systems for liver cancer therapy and diagnosis. The negative consequences of individual nanocarrier in the drug delivery system will also not be covered in this review.

Oral Delivery of Anticancer Agents Using Nanoparticulate Drug Delivery System.

Conventionally, anti-cancer agents were administered through the intravenous route. The major drawbacks associated with the intravenous route of administration are: severe side effects, need of hospitalization, nursing care, and palliative treatment. In order to overcome the drawbacks associated with the intravenous route of administration, oral delivery of anti-cancer agents has gained tremendous interest among the scientific fraternity. Oral delivery of anti-cancer agents principally leads to a reduction in the overall cost of treatment, and aids in improving the quality of life of patients. Bioavailability of drugs and inter-subject variability are the major concerns with oral administration of anti-cancer agents. Factors viz. physicochemical and biological barriers (pre-systemic metabolism and transmembrane efflux of the drug) are accountable for hampering oral bioavailability of anti-cancer agents can be efficiently overcome by employing nanocarrier based drug delivery systems. Oral delivery of anticancer agents by employing these drug delivery systems will not only improve the quality of life of patients but will also provide pharmacoeconomic advantage and lead to a reduction in the overall cost of treatment of life-threatening disease like cancer. This article aims to familiarize the readers with some of the recent advancements in the field of nanobased drug delivery systems for oral delivery of anticancer agents. Advancement in the field of nanotechnology-based drug delivery systems has opened up gateways for the delivery of drugs that are difficult to administer orally. Oral delivery of anti-cancer agents by these drug delivery systems will not only improve the quality of life of patients but will also provide pharmacoeconomic advantage and lead to a reduction in the overall cost of treatment of life-threatening disease like cancer.

A Review on Delivery of Anti-Cancer Drugs by Smart Nanocarriers: Data Obtained from Past One Decade

Problems associated with the administration of anticancer drugs, such as limited solubility, poor biodistribution, lack of selectivity, and healthy tissue damage, can be overcome by the implementation of Smart Drug Delivery Systems (SDDSs). Nonspecific distribution and uncontrollable release of drugs in conventional drug delivery systems (CDDSs) have led to the development of smart nanocarrier-based drug delivery systems, which are also known as Smart Drug Delivery Systems (SDDSs). SDDSs can deliver drugs to the target sites with reduced dosage frequency and in a spatially controlled manner to mitigate the side effects experienced in CDDSs. Chemotherapy is widely used to treat cancer, which is the secondly leading cause of death worldwide. Sitespecific drug delivery led to a keen interest in the SDDSs as an alternative to chemotherapy. A smart drug delivery system consists of smart nanocarriers, targeting mechanisms, and stimulus techniques. This review highlights the recent development of SDDSs for a number of smart nanocarriers, including liposomes, micelles, den-drimers, meso-porous silica nanoparticles, gold nanoparticles, super paramagnetic iron-oxide nanoparti-cles, carbon nanotubes, and quantum dots. The nanocarriers are described in terms of their structures, classification, synthesis and degree of smartness.

Various Challenges and Opportunities in Oral Delivery of Anticancer Drugs

Oncology is that area of medicine where patients are usually treated intravenously. Researchers are trying to find alternative drug delivery methods of anticancer drugs due to the pain associated with conventional drug delivery methods. Studies estimate that a majority of patients (up to 89%) prefer oral anticancer medications to traditional IV fluid or injection therapies when available. Better patient compliance, tolerability, reduced cost; greatest safety and possible increased efficacy are the main reasons for increased attention towards oral delivery of anti-cancer drugs. But oral bioavailability of this class is limited because of its idiosyncratic physicochemical properties and biological barriers such as pre-systemic metabolism and gastrointestinal instability. The various challenges to oral delivery of anticancer drugs are discussed extensively in this paper including peculiar physicochemical properties, biological barriers and adverse drug-drug interactions. Further, the emerging innovations in addressing the challenges to oral delivery of anticancer drugs are discussed. These mainly include absorption enhancers and nanocarriers based drug delivery systems.

Biomimetic nanostructures/cues as drug delivery systems: a review

With key scientific advances, researchers are now able to understand biological structures shapes, processes, and mechanisms. The exploitation of these biological fundamentals is a growing area of biomedical research to produce highly efficient and eco-friendly solutions to offer better health facilities. In recent years, the use of naturally inspired structures and processes have gained high research interests to develop numerous types of drug delivery systems (DDSs) to tackle various diseases of high concern. Biologically inspired materials along with both internal and external stimuli-responsive behaviors can be used to engineer advanced DDSs, the so-called ‘smart DDS.’ Biobased constructs with biomedical potentialities either resemble biological structures to produce similar kind of response or synthesize using a biologically inspired process to avoid their possible failure or rejection. Several DDSs have shown great potential for successful treatment of diseases by specific targeting to diseased tissue with enhanced drug efficiency, bioavailability, and biocompatibility. Subject to the application type and purpose, the nanocarrier-based DDSs are considered potential candidates to deliver biopharmaceuticals. Herein, we reviewed the biomimicry of various DDSs at the nanoscale. Emphasis is given to the DDS based on nanoparticles, nanofibers, micelles, liposomes, and hydrogels. The biomimicry of each of the aforementioned DDSs has also been highlighted, with respect to their action mechanisms and use as novel carriers for biomedical applications at large and drug delivery, in particular.

A dual-functional HER2 aptamer-conjugated, pH-activated mesoporous silica nanocarrier-based drug delivery system provides in vitro synergistic cytotoxicity in HER2-positive breast cancer cells.

Purpose: As well as functioning as a ligand that is selectively internalized by cells overexpressing human epidermal growth factor receptor-2 (HER2), HApt can exert cytotoxic effects by inducing cross-linking and subsequent translocation of HER2 to cytoplasmic vesicles, such downregulation of HER2 inhibits cell proliferation and induces apoptosis. We aimed to exploit the potential of HApt as both a targeting agent and antagonist to maximize the efficacy of mesoporous silica nanoparticle (MSN)-based drug release systems for HER2-positive breast cancer.Materials and methods: We fabricated novel HApt aptamer-functionalized pH-sensitive β-cyclodextrin (β-CD)-capped doxorubicin (DOX)-loaded mesoporous silica nanoparticles (termed MSN-BM/CD-HApt@DOX) for targeted delivery and selective targeting of HER2-positive cells. MSN-functionalized benzimidazole (MSN-BM) was used to load and achieve pH stimuli-responsive release of the chemotherapeutic agent doxorubicin (DOX). β-cyclodextrin was introduced as a gatekeeper for encapsulated DOX and HApt as a selective HER2-targeting moiety and biotherapeutic agent.Results: Physical and chemical characterizations (FT-IR, XRD, TEM and BET) confirmed successful construction of MSN-BM/CD-HApt@DOX nanoparticles. In vitro release assays verified pH-sensitive DOX release. MSN-BM/CD-HApt@DOX (relative DOX concentration, 3.6 μg/mL) underwent HER2-mediated endocytosis and was more cytotoxic to HER2-positive SKBR3 cells than HER2-negative MCF7 cells. MSN-BM/CD-HApt@DOX also exhibited better uptake and stronger growth inhibition in SKBR3 cells than the control MSN-BM/CD-NCApt@DOX functionalized with a scrambled nucleotide sequence on CD. Overall, intracellular delivery of DOX and the biotherapeutic agent HApt resulted in synergistic cytotoxic effects in HER2-positive cancer cells in comparison to either DOX or HApt alone.Conclusion: MSN-BM/CD-HApt@DOX enables HER2-mediated targeting and biotherapeutic effects as well as pH-responsive DOX drug release, resulting in synergistic cytotoxic effects in HER2-overexpressing cells in vitro. This novel nanocarrier could potentially enable specific targeting to improve the efficacy of chemotherapy for HER2-positive cancer.

Nanoparticle Based Treatment for Cardiovascular Diseases.

Nanotechnology has gained increased attention for delivering therapeutic agents effectively to the cardiovascular system. Heart targeted nanocarrier based drug delivery is a new, effective and efficacious approach for treating various cardiac related disorders such as atherosclerosis, hypertension, and myocardial infarction. Nanocarrier based drug delivery system circumvents the problems associated with conventional drug delivery systems, including their nonspecificity, severe side effects and damage to the normal cells. Modification of physicochemical properties of nanocarriers such as size, shape and surface modifications can immensely alter its invivo pharmacokinetic and pharmacodynamic data and will provide better treatment strategy. Several nanocarriers such as lipid, phospholipid nanoparticles have been developed for delivering drugs to the target sites within the heart. This review summarizes and increases the understanding of the advanced nanosized drug delivery systems for treating cardiovascular disorders with the promising use of nanotechnology.

A Brief Review on Therapeutic Potential of Nanocarrier Systems Against Breast Cancer

Now a day’s breast cancer is one of the major type of non-cutaneous cancer occurred in female bodies. There are many approaches to treat this type of cancer, but significant treatments for breast cancer are truly limited. Not only the existing treatments are very low in number, but they have number of toxicity issues also. That is why now nano carrier based approaches are under the spot light and researchers are trying to explore this novel area of treatment for breast cancer. The success of any anticancer chemotherapy truly depends on the ability of the drug to reach their targeted body site, where the abnormal cell growth has occurred. Conventional types of treatment has no such targeting benefits. The nanocarriers based drug delivery systems are having some great advantages. These carrier systems have great specific targeting ability; they can modify the bio-distributionand pharmacokinetic profiles of the therapeutic agents. That is why nanocarriers are having lesser cytotoxic side effects than the conventional type of treatments. And these benefits make these carrier systems unique. The popular nanocarries used for today are liposomes, carbon nanotubes, micelles, quantum dots, nanoparticles, gold nanoparticles, solid lipid nanoparticles etc. This review is a brief discussion about the nanocarriers used for breast cancer today and their advancements.

A Brief Review on Therapeutic Potential of Nanocarrier Systems Against Breast Cancer

Now a day’s breast cancer is one of the major type of non-cutaneous cancer occurred in female bodies. There are many approaches to treat this type of cancer, but significant treatments for breast cancer are truly limited. Not only the existing treatments are very low in number, but they have number of toxicity issues also. That is why now nano carrier based approaches are under the spot light and researchers are trying to explore this novel area of treatment for breast cancer. The success of any anticancer chemotherapy truly depends on the ability of the drug to reach their targeted body site, where the abnormal cell growth has occurred. Conventional types of treatment has no such targeting benefits. The nanocarriers based drug delivery systems are having some great advantages. These carrier systems have great specific targeting ability; they can modify the bio-distributionand pharmacokinetic profiles of the therapeutic agents. That is why nanocarriers are having lesser cytotoxic side effects than the conventional type of treatments. And these benefits make these carrier systems unique. The popular nanocarries used for today are liposomes, carbon nanotubes, micelles, quantum dots, nanoparticles, gold nanoparticles, solid lipid nanoparticles etc. This review is a brief discussion about the nanocarriers used for breast cancer today and their advancements.

Exploiting Nanomaterial-mediated Autophagy for Cancer Therapy.

Autophagy is a conserved process that is critical for sequestering and degrading proteins, damaged or aged organelles, and for maintaining cellular homeostasis under stress conditions. Despite its dichotomous role in health and diseases, autophagy usually promotes growth and progression of advanced cancers. In this context, clinical trials using chloroquine and hydroxychloroquine as autophagy inhibitors have suggested that autophagy inhibition is a promising approach for treating advanced malignancies and/or overcoming drug resistance of small molecule therapeutics (i.e., chemotherapy and molecularly targeted therapy). Efficient delivery of autophagy inhibitors may further enhance the therapeutic effect, reduce systemic toxicity, and prevent drug resistance. As such, nanocarriers-based drug delivery systems have several distinct advantages over free autophagy inhibitors that include increased circulation of the drugs, reduced off-target systemic toxicity, increased drug delivery efficiency, and increased solubility and stability of the encapsulated drugs. With their versatile drug encapsulation and surface-functionalization capabilities, nanocarriers can be engineered to deliver autophagy inhibitors to tumor sites in a context-specific and/or tissue-specific manner. This review focuses on the role of nanomaterials utilizing autophagy inhibitors for cancer therapy, with a focus on their applications in different cancer types.

Tumor-microenvironment controlled nanomicelles with AIE property for boosting cancer therapy and apoptosis monitoring

Mild acidity matrix, rich blood vessels and special biomarkers constitute the primary tumor microenvironment. Nanoparticles could change their physicochemical characteristics by functionalizing a series of moieties which is responsive towards pH or specific markers. So precise regulation of nanocarrier-based drug delivery systems by the tumor microenvironment has showed great potential for theranostics. Herein, we developed a smart nano delivery system STD-NM, showing tumor microenvironment responsive targeting, efficient drug delivery and precise evaluation of therapeutic effect in vivo. STD-NM kept in ‘stealth’ state in normal environment while ‘activated’ in the tumor acidic environment, which could show stability in blood circulation while deeply penetrate into tumor tissues. Additionally, STD-NM was designed with aggregation-induced emission (AIE) characteristic, of which the fluorescence ‘switch on’ when apoptosis taken place. Gene analysis by RNA-seq also confirmed a superior therapeutic effect of drug loaded STD-NM treatment. We envisioned the well-designed smart nano materials for drug delivery could open a new avenue in precisely tumor imaging and specific cancer therapeutics.