Polymeric nanomaterials have emerged as a promising platform in the field of nanomedicine, specifically in theranostics, where both diagnostic and therapeutic capabilities are combined. With the progress made in therapeutic and diagnostic techniques, there is an urgent need to combine imaging capabilities with these functions into one integrated platform that can evaluate the effectiveness of treatments. By incorporating targeting ligands like antibodies, peptides, or aptamers, these nanomaterials can selectively recognize and image tumors, enabling early detection and accurate diagnosis. Furthermore, they offer various therapeutic interventions such as photothermal therapy, photodynamic therapy, and gene therapy, demonstrating their versatility in synergistic combination therapies and multimodal treatments. The integration of ligands and simultaneous delivery of imaging and pharmaceutical entities seek to facilitate the real-time tracking of disease advancement and treatment effectiveness. Therefore the selection of suitable nanovectors is vital in theranostics, where specific characteristics like biocompatibility, high loading capacity, biodegradability, and surface functionality are essential in the design of nanotheranostic carrier. Here we provide a comprehensive overview of the current status of polymeric nanomaterials and their applications in different theranostic aspects, especially cancer therapy. Besides, the chapter highlights the design principles, synthesis methods, and multifunctional properties, as well as showcasing their potential for precise targeted drug delivery, diagnosis, active monitoring, and effective treatments taking into consideration that polymeric nanomaterials have a significant role in the field of theranostics with a great promise for both personalized and predictive medicine.
The role of nontoxic and biodegradable polymers is crucial not only for the development of drug carriers but also for the synthesis of various medical appliances such as sutures and stents. People around the world suffer from deadly diseases, one of which is cancer. However, the grief of the world has been heard by scientists around the world, leading to the development of new drugs. Even though the drugs have been developed, their absorption, distribution, metabolism, excretion, and toxicity properties remain a concern. Therefore these valuable drugs need to be carried into the body toward the targeted cancer cells using a suitable vehicle. One such kind of drug transporter is polyglutamic acid (PGA). Due to their less cytotoxic behavior toward normal cells, easy degradability, and controlled and prolonged release of drugs through them, they have been chosen as one of the polymers suitable for medical use. This chapter deals with the synthesis and various applications of PGA in the field of medical science.
Cancer is one of the most devastating illnesses that has become the second most deadly disease all over the world. Advancements in current therapies including surgery, radiotherapy, chemotherapy, and understanding of tumor biology have achieved clinical management of cancer to some extent but the threat is still there and giving the alarming signs. Even though patient survival rates have increased, metastasis and other late-stage diagnosed tumors are still linked to high 5-year mortality rates. Therapeutic oligonucleotides (TOs) that have been proven most promising in many serious illnesses are also becoming a crucial part of cancer therapeutics, specifically for undruggable targets, due to their specificity at the molecular level modulation of gene expression responsible for the disease. The entire therapeutic potential of these oligonucleotides depends on their safe and efficient delivery. Chitosan has been well investigated for its advantages in gene therapy and favored over other polymers due to its biocompatibility, biodegradability, and tunable functional groups that can be tailored for targeting via specific agents. In this chapter, we discussed the studies of chitosan nanoparticles for the delivery of oligonucleotides and in disease diagnosis as well.
Liposomes are vesicles constituted by phospholipids that are used as drug carrier systems for hydrophilic and lipophilic substances, enabling the encapsulation of different types of anticancer drugs within their structure. Through molecules attached to their surface, liposomes can promote the targeting and release of antineoplastic agents in specific tissues, which guarantees drug efficacy, reducing toxicity to healthy tissues. Since their discovery, liposomes have become a useful device in drug delivery, due to their resemblance to natural cells and vesicles, and have also been used in studies of membrane proteins and synthetic organisms.
Polymeric micelles because of their distinct advantages are attractive vehicles for tumor-targeted delivery of anticancer drugs. Polymeric micelles are formed by self-assembly of amphiphilic block copolymers and have specific core–shell architecture. Further, polymeric micelles serve as powerful tools to combat multidrug resistance (MDR), a dominant hindrance in chemotherapy. The various strategies of polymeric micelles to overcome MDR include codelivery of therapeutic agent and a P-gp inhibitor or siRNA or an antiapoptotic protein, enhanced intracellular drug concentrations utilizing stimuli-sensitive drug release, combination therapies like chemo-phototherapy which sensitizes the resistant cancer cells. The ability of tumor-targeted delivery of polymeric micelles also bestows them diagnostic/imaging applications (by encapsulating diagnostic/imaging agents), visualization of therapy is made possible because of theranostic application of polymeric micelles, wide applicability in combinatorial therapy of which include multidrug therapy, chemo-gene therapy, chemo-phototherapy, etc. The efficiency of polymeric micelles is evidenced by the formulations like Genexol (marketed micellar formulation of paclitaxel) and a series of formulations in clinical trials.
The use of poly(d,l-lactic acid) (PLA)-based systems in drug and gene delivery for cancer treatment holds significant promise. PLA is a biocompatible and biodegradable polymer that can be derived from renewable resources, making it environmentally friendly. Its advantageous properties, including tunable degradation rates and encapsulation capabilities, enable controlled release of therapeutics and targeted delivery to tumor sites. PLA-based carriers protect genetic materials and facilitate gene therapy, offering precise and personalized cancer treatment. Strategies such as surface modifications and combination with other materials enhance delivery efficiency. While PLA-based micro and nanoparticles have shown great potential in biomedical applications, they may have drawbacks like initial burst release. Nevertheless, PLA remains highly flexible, allowing for precise control over physical properties for desired pharmacokinetics. Overall, this chapter presents an overview of the synthesis, modifications, and applications of PLA for drug and gene delivery in cancer research, showcasing its potential in enhancing biomedical applications. Additionally, the chapter discusses the challenges and future prospects of PLA-based delivery systems in the context of personalized medicine and gene therapy. By providing a comprehensive overview of the use of PLA in drug and gene delivery, this chapter aims to highlight its potential impact on the advancement of therapeutic strategies.
In the last few decades, nanotechnology has been established in all prospects of development. Applications of nanotechnology are also paving new paths for identifying and refining unexplored aspects. Also, progress in nanotechnology has improved the economic progress of development at a global level. Nanomaterials made using this technology can be of many types such as metals, metal oxides, liposomes, dendrimers, nanotubes, fullerenes, quantum dots, and polymeric. Out of these varieties, polymeric nanomaterials are of earnest interest due to their benefits in favor of biological systems. Herein, we highlight poly(alkyl cyanoacrylate) (PACA), a monomer that can be polymerized and used in the synthesis of nanoformulations. PACA nanoformulations were the first synthetic polymer-based structures that are widely used as drug delivery agents and are currently in clinical trials. Thus, this chapter brings into consideration the use of PACA as a compound that can be modified to be used robustly in different fields.
Cancer is a disease which remains the second largest cause of deaths worldwide, this disease is characterized with the uncontrolled cell growth and development. Chemotherapy is considered as the major approach for cancer treatment but this approach lacks the specificity to target cancer cells and avoid normal cells. On the other hand, nanotechnological interventions can overcome the challenges attributed to chemotherapeutic drugs such as unspecific biodistribution, undesired side effects and drug resistance. Nanoparticles can achieve selective accumulation in the target sites through passive or ligand-based targeting mechanisms. Polymer-based nanomedicine involves utilizing a variety of polymeric structures, such as polymeric nanoparticles, polymeric hybrids, polyplexes, and polymeric conjugates. Furthermore, approaches offer opportunities for additional modifications to improve efficiency and reduce anticipated adverse reactions.
Drug discovery is only half the battle won. It needs to be delivered at the right location, in the correct amount for the optimal period without harming the unintended cells of the body. This is crucial for the success of personalized and precision medicine which is shaping the new landscape of cancer treatment. There are several polymers, nanocomposites, and nanoparticles that have been developed as drug delivery agents. In this chapter, we will focus on one such polymer which has been successfully employed for delivery of drugs, protein, and DNA. Poly lactic-co-glycolic acid (PLGA) is one of the few polymers that has been approved by the United States Food and Drug Administration (USFDA) for human administration. It is one of the most widely used biodegradable materials in drug delivery and tissue engineering applications. This chapter will be specific for the application of PLGA in oncology. We discussed the basics of PLGA properties followed by its specific use as delivery agent for chemotherapeutic drugs. Mechanism of action of these formulations is reviewed, followed by comprehensive details of the delivery of individual chemotherapeutic drugs. Combinations are always needed to address complex problems like cancer. We discuss PLGA combination with other nanotechnology-based delivery agents. Finally, we provide future directions and touch upon the debatable toxicity of PLGA-based formulations.
The increase in cases of drug resistance in cancer patients has flooded the market with a huge number of therapeutical approaches. However, resistance to many conventional therapies has yet not been eradicated. Thus the use of nanomedicine has been implemented for the eradication of some of the crucial diseases and infections, as cases of resistance to nanoparticles are rare. Dendrimers are one such type of special nano construct that unlike other nanomaterials have large internal space and outer surface area that are attached to various functional groups that can carry a considerable number of ligands attached to them and even encapsulated drugs. In this chapter, various biomedical applications and in vitro and in vivo studies have been discussed, indicating the properties of dendrimers as an excellent drug carrier for the treatment of cancer in future.
With the advent of vaccines against covid-19, nanoparticles-based nonviral vectors have gained more attention in the areas of pharmaceutics, diagnosis, and therapeutics. Nanoparticles can be used as potent drug, as well as carrier of drugs due to their unique physico-chemical properties like small size and thus more surface area to mass ratio, and can easily be engineered to have specific targeted delivery. Eventually, the inclusion of nanoparticles not only provides robust pharmaceutic platform for various medical applications, they will also help in reducing the economic burden of our healthcare system. More understanding is required in terms of characterization, modifications, storage, quality control, and biological applications of the nanoparticles. Profound investigations to understand their mechanism of action on living organisms including humans and detailed policy for their moderate usage with compliance to medical ethics are the need of the hour.
Lipid-based nanoparticles are one of the widely used drug delivery systems for cancer treatment. Lipid nanoparticles, constituted with different chemical composition, are considered versatile carriers to deliver various bioactive molecules and thus have garnered interests in cancer treatment. Herein, we provide a broad review of lipid nanoparticle formulations and discuss their production methods, surface modifications, active and passive targeting to cancer, and their pros and cons for clinical application. Barriers that lipid nanoparticles face when in physiological conditions, which impose challenges to clinical translation, are also discussed. Despite the hurdles, lipid-based nanoparticles have remained the frontrunner and the most widely tested drug carrier for cancer therapy. Currently there are few lipid-based drugs approved by Federal Drug Administration for cancer therapy and more than 400 lipid nanoparticle-based cancer therapy studies in clinical trials, which is accompanied with thousands of peer-reviewed papers being published yearly.
Polyamine acid, which is made up of numerous amino acid residues, demonstrates desirable qualities with excellent coordinated biocompatibility with different forms and compositions. Among the several, polyamine acids nowadays receive a lot of eyes because of their outstanding performance in many fields, not just food preservation. This chapter will be holding recent and latest updates regarding poly-l-lysine (PLL) with its application and future prospects. Basically, throughout the years since their discovery, PLL has been used as delivery agents for drugs, DNA, adjuvants, or carriers, but with recent integrative knowledge of pharmacokinetics and pharmacodynamics of drug systems, designing and synthesis can also be manipulated with PLL. Furthermore, the results of combining lysine-based polymers with other cutting-edge techniques and technologies showed that difficulties like scale production and high costs would not stand in the way of their potential future.
Cancer cases menace people around the world with a total number of 19,288,916 new cancer cases and 9,956,108 mortalities, which may increase by 30 million new cases by 2040. Apart from exposure to carcinogens, the change in lifestyle, directly and indirectly, has a great impact on the environment. Extreme climatic conditions, and alterations in the environment, have led to an increase in the number of cancer cases due to both biotic and abiotic factors. Genetic mutations in organisms both in the host and the causal organism such as some viruses and other microorganisms, have also contributed to global cancer increase. Therefore researchers have contributed to the ever-evolving process of medication and therapeutics, which may target the root cause of cancer and ultimately decrease mortality and morbidity. Among modern cancer treatments, nanotechnology is the upcoming field that has been explored by researchers. Different nanoparticles of various sizes and shapes have been examined for the cure and delivery of various anticancerous drugs. Thus removing the drug resistance barrier in most cancerous cells improves therapy.
Gadd45 genes have been implicated in stress signaling responses to various physiological or environmental stressors, resulting in cell cycle arrest, DNA repair, cell survival and senescence, or apoptosis. Evidence accumulated up to date suggests that Gadd45 proteins function as stress sensors, mediating their activity through a complex interplay of physical interactions with other cellular proteins that are implicated in cell cycle regulation and the response of cells to stress. These include PCNA, p21, cdc2/cyclinB1, and the p38 and JNK stress response kinases. Disregulated expression of Gadd45 has been observed in multiple types of solid tumors as well as in hematopoietic malignancies. Also, evidence has accumulated that Gadd45 proteins are intrinsically associated with the response of tumor cells to a variety of cancer therapeutic agents. Thus, Gadd45 proteins may represent a novel class of targets for therapeutic intervention in cancer. Additional research is needed to better understand which of the Gadd45 stress response functions may be targeted for chemotherapeutic drug design in cancer therapy.
Local radiotherapy is the treatment of choice for solitary bone plasmacytoma (SBP) and the role of adjuvant systemic chemotherapy in preventing progression to multiple myeloma (MM) is controversial. The purpose of this study was to examine the presence of systemic disease in the form of neoplastic plasma cells (PC) in bone marrow of patients with SBP. Flow cytometric immunophenotyping of PC was carried out on bone marrow aspirate of 7 patients using monoclonal antibodies: CD19 FITC, CD45 FITC, CD20 FITC, CD52 PE, CD117 PE, CD56 PE, CD38 PerCP-Cy5.5, CD138 APC, anti-kappa (κ) FITC and anti-lambda (λ) PE. The neoplastic as well as normal PC were identified in bone marrow aspirate of all the patients at the time of diagnosis; the neoplastic PC ranged from 0.1%to 0.7% of all BM cells and 33.5% to 89.7% of total BMPC. The κ:λ ratio was normal in all the samples ranging from 0.5% to 1.6%. The present work shows the presence of systemic disease in the form of neoplastic PC in bone marrow of patients with SBP. Prospective studies would be required to study if the levels of neoplastic PC in the bone marrow may help us identify patients who are likely to progress to overt MM and benefit from systemic chemotherapy.
