Smart Nanotherapeutics and Lung Cancer

Lung cancer is a significant health problem worldwide. Unfortunately, current therapeutic strategies lack a sufficient level of specificity and can harm adjacent healthy cells. Consequently, to address the clinical need, novel approaches to improve treatment efficiency with minimal side effects are required. Nanotechnology can substantially contribute to the generation of differentiated products and improve patient outcomes. Evidence from previous research suggests that nanotechnology-based drug delivery systems could provide a promising platform for the targeted delivery of traditional chemotherapeutic drugs and novel small molecule therapeutic agents to treat lung cancer cells more effectively. This has also been found to improve the therapeutic index and reduce the required drug dose. Nanodrug delivery systems also provide precise control over drug release, resulting in reduced toxic side effects, controlled biodistribution, and accelerated effects or responses. This review highlights the most advanced and novel nanotechnology-based strategies, including targeted nanodrug delivery systems, stimuli-responsive nanoparticles, and bio-nanocarriers, which have recently been employed in preclinical and clinical investigations to overcome the current challenges in lung cancer treatments.

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Paclitaxel-Loaded and Folic Acid Modified PLGA Nanomedicine with Glutathione-Response for the Treatment of Lung Cancer

10.21203/rs.3.rs-30586/v1 ◽

2020 ◽

Author(s):

Zhanxia Zhang ◽

Wang Yao ◽

Jialiang Yao ◽

Fangfang Qian ◽

Zujun Que ◽

...

Keyword(s):

Lung Cancer ◽

Folic Acid ◽

Side Effects ◽

Targeted Delivery ◽

Great Promise ◽

Stimuli Responsive ◽

Biologically Relevant ◽

Chemotherapy Agents

Abstract Targeted delivery and smart response of nanomedicine hold great promise to improve the therapeutic efficacy and alleviate the side effects of chemotherapy agents in cancer treatment. While a few research systems about organic nanomedicines with these properties have limited the development prospect of nanomedicines. In the present study, folic acid (FA) targeted delivery and GSH (glutathione) smart responsive nanomedicine was rationally designed for paclitaxel (PTX) delivery in the treatment of lung cancer. Compared with other stimuli responsive nanomedicines, this nano-carrier was not only sensitive to biologically relevant GSH for on demand drug release but also biodegradable into biocompatible by products after fulfilling its delivering task. The nanomedicine can firstly enter into tumor cells via FA and its receptor mediated endocytosis. After lysosomes escape, the PLGA (poly(lactic-co-glycolic acid) nanomedicine was triggered by the higher level of GSH and released its cargo in tumor microenvironment. In vitro and in vivo results revealed that the PLGA nanomedicine not only can inhibit the proliferation and promote the apoptosis of lung cancer cells greatly, but also possesses less toxic side effects when compared with free PTX. Therefore, the proposed drug delivery system demonstrates the encouraging potential for multifunctional nano-platform applicable to enhance the bioavailability and reduce the side effects of chemotherapy agents.

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Improved Therapeutic Efficacy of Topotecan Against A549 Lung Cancer Cells with Folate-targeted Topotecan Liposomes

Current Drug Metabolism ◽

10.2174/1389200221999200820163337 ◽

2020 ◽

Vol 21 (11) ◽

pp. 902-909

Author(s):

Jingxin Zhang ◽

Weiyue Shi ◽

Gangqiang Xue ◽

Qiang Ma ◽

Haixin Cui ◽

...

Keyword(s):

Lung Cancer ◽

Drug Delivery ◽

Cancer Cells ◽

Targeted Delivery ◽

Therapeutic Efficacy ◽

Drug Delivery Systems ◽

Lung Tumor ◽

A549 Cells ◽

Delivery Systems ◽

Lung Cancer Cells

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

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Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy

Current Drug Targets ◽

10.2174/1389450121666200514222900 ◽

2020 ◽

Vol 21 (11) ◽

pp. 1084-1098

Author(s):

Fengqian Chen ◽

Yunzhen Shi ◽

Jinming Zhang ◽

Qi Liu

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Cancer Therapy ◽

Drug Delivery Systems ◽

Therapeutic Index ◽

Delivery Systems ◽

Epigenetic Therapy ◽

Cancer Therapies ◽

Therapeutic Benefits ◽

High Therapeutic Index

This review summarizes the epigenetic mechanisms of deoxyribonucleic acid (DNA) methylation, histone modifications in cancer and the epigenetic modifications in cancer therapy. Due to their undesired side effects, the use of epigenetic drugs as chemo-drugs in cancer therapies is limited. The drug delivery system opens a door for minimizing these side effects and achieving greater therapeutic benefits. The limitations of current epigenetic therapies in clinical cancer treatment and the advantages of using drug delivery systems for epigenetic agents are also discussed. Combining drug delivery systems with epigenetic therapy is a promising approach to reaching a high therapeutic index and minimizing the side effects.

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Cancer Nanotechnology-An Excursion on Drug Delivery Systems

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180720164015 ◽

2019 ◽

Vol 18 (15) ◽

pp. 2078-2092 ◽

Cited By ~ 2

Author(s):

Mala Sharma ◽

Chitranshu Pandey ◽

Neha Sharma ◽

Mohammad A. Kamal ◽

Usman Sayeed ◽

...

Keyword(s):

Drug Delivery ◽

Targeted Delivery ◽

Drug Delivery Systems ◽

Cancer Chemoprevention ◽

Delivery Systems ◽

Nanostructured Lipid Carrier ◽

Nanodrug Delivery ◽

Drug Conjugates ◽

Drug Nanoparticles ◽

Cancer Nanotechnology

Background: Nanotechnology pictures a breakthrough in the domain of cancer therapy owing to its novel properties and functions. This technology is quite amendable as it allows the scientists to engineer drug nanoparticles of dimensions 10nm – 500nm permitting them to pass via leaky vasculature of tumorigenic microenvironment with higher specificity, reduced cytotoxicity and effective release without any after effects. The central part of the review zooms onto the role of nanoparticles and their targeted delivery for the cure of cancer. Methods: The novel and various versatile nanoparticle platforms viz. polymeric (drug-conjugates, micelles, dendrimers), Lipid-based (liposomes, solid nanoparticle, nanostructured lipid carrier, lipid-polymer hybrid), and stimuli-sensitive (thermoresponsive, ultrasound, pH-responsive, hydrogel) etc. have been designed for a persistent, précised nanodrug delivery and the co-delivery of collegial drug conjugates leading to the formation of safer release of myriad of drugs for cancer chemoprevention. Results: The review concerns about tracing and detailing the drug delivery systems of cancer nanotechnology. Conclusion: Nanotechnology is bestowed with the design, depiction, fabrication, and application of nanostructures, and devices with their controlled delivery together with the imaging of the selected target site and drug release at the specific site of action.

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The Nanosystems Involved in Treating Lung Cancer

Life ◽

10.3390/life11070682 ◽

2021 ◽

Vol 11 (7) ◽

pp. 682

Author(s):

Andreea Crintea ◽

Alina Gabriela Dutu ◽

Gabriel Samasca ◽

Ioan Alexandru Florian ◽

Iulia Lupan ◽

...

Keyword(s):

Lung Cancer ◽

Side Effects ◽

Chromosomal Rearrangements ◽

Sirna Delivery ◽

Delivery Systems ◽

Inorganic Nanoparticles ◽

New Methods ◽

Different Types ◽

Or Gene ◽

The Many

Even though there are various types of cancer, this pathology as a whole is considered the principal cause of death worldwide. Lung cancer is known as a heterogeneous condition, and it is apparent that genome modification presents a significant role in the occurrence of this disorder. There are conventional procedures that can be utilized against diverse cancer types, such as chemotherapy or radiotherapy, but they are hampered by the numerous side effects. Owing to the many adverse events observed in these therapies, it is imperative to continuously develop new and improved strategies for managing individuals with cancer. Nanomedicine plays an important role in establishing new methods for detecting chromosomal rearrangements and mutations for targeted chemotherapeutics or the local delivery of drugs via different types of nano-particle carriers to the lungs or other organs or areas of interest. Because of the complex signaling pathways involved in developing different types of cancer, the need to discover new methods for prevention and detection is crucial in producing gene delivery materials that exhibit the desired roles. Scientists have confirmed that nanotechnology-based procedures are more effective than conventional chemotherapy or radiotherapy, with minor side effects. Several nanoparticles, nanomaterials, and nanosystems have been studied, including liposomes, dendrimers, polymers, micelles, inorganic nanoparticles, such as gold nanoparticles or carbon nanotubes, and even siRNA delivery systems. The cytotoxicity of such nanosystems is a debatable concern, and nanotechnology-based delivery systems must be improved to increase the bioavailability, biocompatibility, and safety profiles, since these nanosystems boast a remarkable potential in many biomedical applications, including anti-tumor activity or gene therapy. In this review, the nanosystems involved in treating lung cancer and its associated challenges are discussed.

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Onco-Receptors Targeting in Lung Cancer via Application of Surface-Modified and Hybrid Nanoparticles: A Cross-Disciplinary Review

Processes ◽

10.3390/pr9040621 ◽

2021 ◽

Vol 9 (4) ◽

pp. 621

Author(s):

Fakhara Sabir ◽

Maimoona Qindeel ◽

Mahira Zeeshan ◽

Qurrat Ul Ain ◽

Abbas Rahdar ◽

...

Keyword(s):

Lung Cancer ◽

Targeted Delivery ◽

Current Knowledge ◽

Folate Receptor ◽

Delivery Systems ◽

Chemotherapeutic Agents ◽

The Body ◽

Hybrid Nanoparticles ◽

Wide Range ◽

Surface Modified

Lung cancer is among the most prevalent and leading causes of death worldwide. The major reason for high mortality is the late diagnosis of the disease, and in most cases, lung cancer is diagnosed at fourth stage in which the cancer has metastasized to almost all vital organs. The other reason for higher mortality is the uptake of the chemotherapeutic agents by the healthy cells, which in turn increases the chances of cytotoxicity to the healthy body cells. The complex pathophysiology of lung cancer provides various pathways to target the cancerous cells. In this regard, upregulated onco-receptors on the cell surface of tumor including epidermal growth factor receptor (EGFR), integrins, transferrin receptor (TFR), folate receptor (FR), cluster of differentiation 44 (CD44) receptor, etc. could be exploited for the inhibition of pathways and tumor-specific drug targeting. Further, cancer borne immunological targets like T-lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and dendritic cells could serve as a target site to modulate tumor activity through targeting various surface-expressed receptors or interfering with immune cell-specific pathways. Hence, novel approaches are required for both the diagnosis and treatment of lung cancers. In this context, several researchers have employed various targeted delivery approaches to overcome the problems allied with the conventional diagnosis of and therapy methods used against lung cancer. Nanoparticles are cell nonspecific in biological systems, and may cause unwanted deleterious effects in the body. Therefore, nanodrug delivery systems (NDDSs) need further advancement to overcome the problem of toxicity in the treatment of lung cancer. Moreover, the route of nanomedicines’ delivery to lungs plays a vital role in localizing the drug concentration to target the lung cancer. Surface-modified nanoparticles and hybrid nanoparticles have a wide range of applications in the field of theranostics. This cross-disciplinary review summarizes the current knowledge of the pathways implicated in the different classes of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. Furthermore, it focuses specifically on the significance and emerging role of surface functionalized and hybrid nanomaterials as drug delivery systems through citing recent examples targeted at lung cancer treatment.

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Novel Approaches for Efficient Delivery of Tyrosine Kinase Inhibitors

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps29891 ◽

2019 ◽

Vol 22 ◽

pp. 37-48 ◽

Cited By ~ 1

Author(s):

Zahra Moradpour ◽

Leila Barghi

Keyword(s):

Side Effects ◽

Tyrosine Kinase ◽

Dissolution Rate ◽

Targeted Delivery ◽

Kinase Inhibitors ◽

Delivery Systems ◽

Chemotherapeutic Agents ◽

Amorphous Solid Dispersion ◽

Crystal Modification ◽

Particle Size Reduction

Epidermal growth factor receptors (EGFRs) have potential to be considered as therapeutic target for cancer treatment especially in cancer patients with overexpression of EGFR. Cetuximab as a first monoclonal antibody and Imatinib as the first small molecule tyrosine kinase inhibitor (SMTKI) were approved by FDA in 1998 and 2001. About 28 SMTKIs have been approved until 2015 and a large number of compound with kinase inhibitory activity are at the different phases of clinical trials. Although Kinase inhibitors target specific intracellular pathways, their tissue or cellular distribution are not specific. So treatment with these drugs causes serious dose dependent side effects. Targeted delivery of kinase inhibitors via dendrimers, polymeric nanoparticles, magnetic nanoparticles and lipid based delivery systems such as liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) can lead to reduction of side effects and improving therapeutic efficacy of the drugs in the target organs. Furthermore formulation of these drugs is challenged by their physicochemical properties such as solubility and dissolution rate. The main approaches in order to increase dissolution rate, are particle size reduction, self-emulsification, cyclodextrin complexation, crystal modification and amorphous solid dispersion. Synergistic therapeutic effect, decreased side effects and drug resistant, reduced cost and increased patient compliance are the advantages associated with using combination therapy especially in the treatment of cancer. Combination of TKIs with chemotherapeutic agents or biopharmaceuticals such as monoclonal antibodies and oligonucleotides and also combination of two TKIs within one formulation is possible by new targeting delivery systems. This article reviews the recent advances in the design and development of delivery systems for TKIs.

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Targeted Drug Delivery Systems for the Treatment of Glaucoma: Most Advanced Systems Review

Polymers ◽

10.3390/polym11111742 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1742 ◽

Cited By ~ 2

Author(s):

Olga Cegielska ◽

Paweł Sajkiewicz

Keyword(s):

Drug Delivery ◽

Side Effects ◽

Targeted Delivery ◽

Drug Targets ◽

Drug Delivery Systems ◽

Release Kinetics ◽

Controlled Drug Release ◽

Drug Carriers ◽

Delivery Systems ◽

Drug Bioavailability

Each year, new glaucoma drug delivery systems are developed. Due to the chronic nature of the disease, it requires the inconvenient daily administration of medications. As a result of their elution from the eye surface and penetration to the bloodstream through undesired permeation routes, the bioavailability of active compounds is low, and systemic side effects occur. Despite numerous publications on glaucoma drug carriers of controlled drug release kinetics, only part of them consider drug permeation routes and, thus, carriers’ location, as an important factor affecting drug delivery. In this paper, we try to demonstrate the importance of the delivery proximal to glaucoma drug targets. The targeted delivery can significantly improve drug bioavailability, reduce side effects, and increase patients’ compliance compared to both commercial and scientifically developed formulations that can spread over the eye surface or stay in contact with conjunctival sac. We present a selection of glaucoma drug carriers intended to be placed on cornea or injected into the aqueous humor and that have been made by advanced materials using hi-tech forming methods, allowing for effective and convenient sustained antiglaucoma drug delivery.

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How to improve the selectivity of drugs

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf184313_326 ◽

2020 ◽

Vol 18 (4) ◽

Author(s):

Marina A. Dumpis ◽

Marija A. Brusina ◽

Elena V. Litasova ◽

Viktor V. Iljin ◽

Dmitrii N. Nikolayev ◽

...

Keyword(s):

Side Effects ◽

Targeted Delivery ◽

Delivery Systems ◽

High Complexity ◽

Targeted Delivery Systems

The review discusses in detail the causes of side effects of drugs, caused, inter alia, by the high complexity of the organism. The different ways are represented to overcome this problem by creating, in particular, targeted delivery systems. But nevertheless, drugs whose activity is manifested in milligram doses have minimal side effects.

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