The Role of Nanotechnology in Treatment of Cancer

Shaikh Md Moiz*, Shaikh Imran Kalam, Dr.G.J.Khan ,

Aman Shaikh, M Sohil M Shabbir

JIIU’s Ali Allana College of Pharmacy Akkalkuwa, Dist-Nandurbar -425415, Maharashtra, India

*Correspondence: mdmoizshaikh1@gmail.com; Tel.: (+91 9172889819)

INTRODUCTION

The World Health Organisation (WHO) estimated in 2015 that cancer is the first or second leading cause of death before the age of 70 in 91 out of 172 countries, and it ranks as the third or fourth cause of death in an additional 22 countries. Cancer is the second leading cause of death worldwide, and several surgical and therapeutic treatments are available for it, but the traditional conventional treatments, such as chemotherapy, are not only toxic but also have negative side effects.(1) Since targeted therapies are more effective than other treatments (such as regular chemotherapy) and have fewer side effects, such as weaker viability, a reduction in the need for higher doses, a decrease in undesirable side effects, low therapeutic indicators, resistance to multiple drugs, and nonspecific goals, they are the best option among the common cancer treatments.According to recent research, NPs offer several benefits in the diagnosis and treatment of tumours in addition to medications, imaging agents (which may be used for diagnostics), and genes.(2) Nanoparticle-based bioaffinity assays for atomic and cell imaging, directed nanoparticle attached pharmaceuticals for tumour therapy, and integrated nanodevices for early disease screening and identification have all improved as a result of recent developments. Based on the subatomic profiles of individual patients, these developments provide exciting opportunities for customised oncology, where cancer is evaluated and treated using genetic and protein biomarkers. The use of several nanotechnology-based techniques to cancer detection and treatment is included in the current review article. These characteristics might at least ten to one hundred times increase the sensitivity of biological imaging and detection. [8]. Carbon Nanotubes (CNTs) and dendrimers are two examples of other nanomaterials with intriguing features that can be used for cancer treatment, thermal ablation, and drug delivery. The intriguing characteristics of carbon nanotubes (CNTs), which are tubular materials with axial symmetry and widths of nanometres, can be used to diagnose and cure cancer. Similarly, medications might be delivered directly to specific cells and tissues using CNTs One.(1) At the atomic and molecular level, nanotechnology is used to manipulate materials and create structures and systems. These techniques manipulate matter at nearly atomic sizes to create novel or improved goods, gadgets, and materials. Nanotechnology has been around for ages, but until it was introduced by contemporary labs, its possibilities were limited.(11) The development of revusiran, a promising siRNA-N-acetylgalactosamine (GalNAc) ligand conjugate for hereditary transthyretin amyloidosis with cardiomyopathy, was halted due to a higher mortality rate than the placebo group in a phase III trial, which was a significant setback for the field of RNA interference (RNAi). Revusiran-induced higher mortality may be caused by immunological activation, off-target effects, unanticipated on-target effects, and inadequate research design with respect to statistical analysis. Studies on mice have shown that siRNAs can activate Toll-like receptor 3 (TLR3), a sensor for foreign double-stranded RNA, to produce vascular and immunological effects. Nevertheless, it has been demonstrated that chemical changes, like those applied to revusiran, inhibit TLR activation. Additionally, revusiran was developed using design techniques to try to prevent off-target effects. Given the significance of wild type transthyretin in several physiological processes, it is plausible that on-target actions resulting from its suppression might have adverse consequences. The use of constructs with nanoscale dimensions is the common denominator among various definitions of nanotechnology. However, there are three distinct advantages that arise from applying nanotechnology to the treatment of disease. For example, thransthyretin is a carrier for thyroid proteins and retinol-binding proteins in the blood, protects pancreatic β-cells from apoptosis, and exhibits proteolytic activity against amyloid β, apolipoprotein A-I, and amidated neuropeptide. It is unclear whether toxicity will be common for such drugs or limited to specific therapeutic agents/formulations. One is that since nanotherapeutics are considerably smaller than most traditional medications, they may combine a number of functional components, each of which can be customised to add in a unique way to the overall therapeutic activity and safety.(12)

MECHANISM IN NANOTECHNOLOGY IN CANCER

Figure 1. Mechanism Of Nanotechnology In Cancer

Nanogels: Encapsulated doxorubicin is released into the tumour microenvironment when nanogel breaks down in the presence of bacterial lipase. Doxorubicin release was shown to cause cytotoxicity against H22 hepatoma cells in vitro, and this release only took place when bacterial lipase was present.(4)

Polymeric: The formulation of Genexol-PMa paclitaxel-loaded poly(lactic acid)-block-poly(ethylene glycol) nanocarrier, which was created to eliminate the requirement for Cremophor EL, was authorised for commercialisation. Consequently, a variety of issues in nanomedicine may find answers with polymeric-based nanomaterials. For controlled drug release, polymeric materials are most commonly utilised due to their chemical and technological flexibility, biocompatibility, and biodegradability.(14)

Polymeric Material: By using a modular self-assembly technique that makes use of prefunctionalized polymeric materials, the construct was optimised to BIND-014 and a combinatorial library of over 100 self-assembled polymeric targeted nanoparticles with different compositions was produced. These consist of using FDA-approved polymeric materials that have already undergone validation for use in biomedical applications and pharmaceutical product manufacturing.(14)

Quantum Dots: In a similar manner, GNPs were produced using Spirulina subsalsa and Lyngbya majuscule, as well as Quantum Dots (QD) from Azadirachta India. A 3D electrochemical cytosensor based on Ni micropillars, PLGA electrospun nanofibers, and quantum dots was discovered to be advantageous for CT imaging, while the quantum dots were found to be advantageous for fluorescence imaging.

Liposome: According to many publications, liposomes are surfaces that work by concentrating on ligands in a number of ways (1). Instead of enhancing tumour aggregation overall, the binding of targeted ligands is done to promote target cell recognition and a cell's absorption of nanocarriers. According to this theory, ligand-receptor interactions would improve cell internalisation following the escape of guided liposomes into the tumor's interstitial space. (1)

Carbon, silica oxides, metal oxides, nanocrystals, lipids, polymers, dendrimers, quantum dots, and other newly created materials are only a few of the components that have produced several unique instruments during the past few decades. carbon, for instance Given their high variability, chemical stability, and distinctive features—such as highly customisable surface chemistry and high carrier capacity—as well as the potential to incorporate a range of molecules as anticancer therapeutics, nanomaterials with a carbon cage—such as fullerenes, nanodiamonds, and graphene structures—such as carbon nanotubes, nanohorns—have been investigated as drug delivery and other biomedical applications. However, the main focus should be on studying the kinetics, thermodynamics, and mechanism of adsorption/desorption equilibria for potential pharmaceuticals on/from carbon nanomaterials with varying purity in order to provide drug delivery platforms.(14)

NANOTECHNOLOGY IN CANCER ADVANTAGE

Potential advantages of engineered therapeutic nanoparticles include: enhancing therapeutic delivery across biological barriers and compartments; regulating bioactive agent release; enhancing therapeutic efficacy by delivering therapeutics to biological targets selectively; carrying out theranostic functions by integrating simultaneous diagnosis and therapy and multimodal imaging into multifunctional nanoplatforms; and restoring undesirable physicochemical properties of bioactive molecules to desired biopharmacologic profiles. The immune system's activation process against cancer cells is a complex one.There are several clear benefits of using nanomedicine to enhance cancer immunotherapy. When administered in vivo, nanoparticles easily trigger an immune response due to their virus-like size. Macrophages and other antigen-presenting cells (APCs) absorb nanoparticles with or without pegylation or other surface modifications that prevent fouling. The field has already made a concerted effort to reduce this immunological activation. Nonetheless, such immune activation is beneficial and can be used for the creation of medicines in the context of cancer immunotherapy. To improve the immune response, for instance, tumour antigens are delivered to APCs using nanoparticles.(15)  Low bioavailability, ineffective cellular absorption, and/or poor solubility are frequent obstacles in the transport of materials at the small-molecule and nanoscale levels that these kinds of nanotechnology platforms solve.(15) The use of chemotherapeutic medicines is further restricted by factors including inadequate cell delivery, restricted solubility, the drug's incapacity to pass through cellular barriers, and the lack of clinical protocols to combat multidrug resistance (MDR). Scientists have turned their attention to nanotechnology and its developments in cancer treatment as an alternate way to get around the restriction.(1)

NANOTECHNOLOGY IN CANCER DIAGNOSIS

Early cancer detection and precise therapeutic impact monitoring on lesions after cure are critical to improving the effectiveness of cancer treatment. Cancer therapy depends heavily on early diagnosis, and nanotechnology has completely changed cancer diagnostics. For X-ray CT, Liu et al. set up ultra-small nano-dots (NDs), which are single-phased nanomaterials of ternary bimetal sulphide that are safe, degradable, and widely used in nanomedicine. It has been demonstrated that NDs can be quickly contaminated by renal clearance. The metabolic behaviour of the NDs and their reduced noxiousness are observed by biological variables after chemical and X-ray absorption and CT. The decreased graphene oxide (GO) coating's dazzling light immersion and photo-thermal constancy, according to Moon et al., offer a greatly enhanced photo-acoustic (PA) enactment for the arrangement of NRs. Chen et al. claim that a nanosystem made of human serum albumin (HSA) may self-accumulate into immutable nanoparticles (NPs), which reduces toxicity and makes the targeted diseased cells more biocompatible. This nanosystem can be utilised to diagnose and cure cancer cells.(1) These developments in nanotechnology led to a significant breakthrough in identifying and treating cancer. A wide variety of nanoparticles have been produced and assessed for their effective use as medicinal and diagnostic agents throughout the past few decades. Molecular imaging in vivo is currently a primary focus of medical research. Molecular imaging is a rapidly developing discipline that has made early illness identification and staging easier and faster. It has also made image-guided therapy and treatment personalisation possible. Various nanoparticles, including as polymers, liposomes, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, and gold nanoparticles, can be employed as contrast agents for molecular and functional imaging. Nanoparticles must improve contrast quickly and very site-specifically in order to meet the criteria of early detection. An appropriate indication for nanoparticle contrast agents is imaging of angiogenesis and vascularization of tumours. Nontargeted nanoparticle formulations are used for increased permeability and retention (EPR), whereas targeted nanoparticle formulations that bind to activated and proliferating endothelial cells are used to detect tumour malignancy and aggressiveness as well as to characterise mechanistic changes in tumour vascularization and such as vessel maturation during antiangiogenic therapy or vascular inflammation during radiotherapy.(10) Recent developments have led to improvements in directed nanoparticle conjugated pharmaceuticals for tumour therapy, integrated nanodevices for illness detection and early screening, as well as bioaffinity tests for atomic and cell imaging based on nanoparticles.These developments create exciting opportunities for personalised oncology, where cancer is analysed and treated according on the subatomic profiles of specific individuals using genetic and protein biomarkers. This review article gives a general summary of how several nanotechnology-based methods for cancer diagnosis and treatment.(4) Nanomaterials' remarkable behaviour and adaptability are the reason for this advancement in cancer diagnostics. These days, nanotechnology validates cancer imaging at the at the molecular, tissue, and cell levels. Lanthanide-based upconversion nanoparticles are one instance.which use autofluorescence to detect deep tissue by upconverting low-energy photons to high-energy ones.(4) Nanotechnology has advanced to the point that nanoparticle imaging is now feasible. Typically, the NPs' contained fluorescent dye or contrast agent overcomes their solubility and toxicity issues. Therapeutic substances are contained in the core of NPs, whereas antibodies can be attached onto their surface. In clinical applications, "theranostics," or the combination of diagnosis and therapy, makes NPs a priceless tool. As for a sample, Aryal et al. used gadolinium ions and iron oxide nanoparticles to create Magnetic Resonance Imaging (MRI) via the LPNs.(1)

DRUGS

These drug are used:

                                                          Figure 2 . Drugs

MECHANISM OF DRUG

1.      DOXORUBICIN:

Doxorubicin's (DOX) toxicity and mechanisms of action. One important mechanism behind DOX's antitumor impact is its ability to intercalate into the DNA helix and/or bind covalently to proteins involved in transcription and DNA replication. DOX easily diffuses into cancer cells and forms a strong bond with the cytoplasmic proteasome.This is followed by DOX attaching to the proteasomal component and entering the nucleus through nuclear pores to form a DOX proteasome complex. Lastly, DOX breaks away from the proteasome and attaches itself to DNA as it has a higher affinity for DNA than for the proteasome. DOX can interact with mitochondria and bind to cardiolipin to stop mitochondrial creatine kinase (MtCK) from adhering to mitochondrial membranes. The mitochondrial respiratory chain's complex I also promotes DOX redox cycling, which in turn promotes the production of reactive oxygen species (ROS).(17)

                                                             Figure 3: Structure of Doxorubicin

2.      PACLITAXEL:

 Paclitaxel is a member of the tubulin-targeting cytoskeletal medication family. As a result, paclitaxel therapy causes chromosomal segregation and aberrant mitotic spindle assembly, which in turn causes problems in cell division. Because paclitaxel stabilises the microtubule polymer and prevents microtubules from deconstructing, it arrests the cell cycle in the G0/G1 and G2/M stages and kills cancer cells. It is well known that paclitaxel's ability to block the mitotic spindle often depends on how well it suppresses microtubule dynamics.The mechanisms of action of paclitaxel are not limited to microtubule targeting. Following acute paclitaxel therapy, Panis et al.18 found that a robust type 2 helper T-cell (Th2) profile and high interleukin (IL) levels were indicators of immunosuppressive state in breast cancer patients. Paclitaxel was demonstrated to produce reactive oxygen species via enhancing the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which further enhanced its potent anticancer effects. The nonchemotherapeutic modes of action of paclitaxel were identified as antineoplastic. discovered that paclitaxel increased the efficacy of chemotherapy by preventing myeloid-derived suppressor cells from having an immunosuppressive impact. (18)

Figure 4: Structure of Paclitaxel

3.      TAMOXIFEN:

With a molecular weight of 371.524 g/mol, tamoxifen (C26H29NO, TAM) belongs to a class of medications known as selective oestrogen receptor modulators (SERMs). Typically, it takes the form of a fine, white, crystalline powder with no smell that dissolves in ethanol, methanol, or acetone but only faintly dissolves in water.Other physical characteristics of TAM include its sensitivity to UV radiation and hygroscopic tendency at high moisture rates. TAM's therapeutic action primarily relies on blocking the binding of oestrogen to oestrogen receptors, which stops oestrogen from subsequently affecting cellular DNA to cause breast cancer. Although it has no influence on the DNA confirmation form, the TAM may also directly attach to DNA molecules. Additional TAM actions on tumour growth are also documented. By affecting the tumour cells' protein kinase C, low concentrations (in microgrammes) of TAM may have lethal effects and impede cell proliferation. It can control the activity of growth factors that drive breast cancer cell development, including insulin-like growth factor 1 (TGF-1), and those that prevent tumour cell growth, like transforming growth factor B (TGF).(19)   

CONCLUSION:

Traditional cancer diagnosis and therapy had several drawbacks, including ineffectiveness and adverse consequences. As nanotechnology has advanced and been combined with other disciplines, a variety of NPs with varied architectures have been introduced. They all have some benefits. The use of NPs treating in vivo tumours is developing quickly.Because of their flexibility, safety, biodegradation, and biocompatibility, nanomaterials have shown great promise.

Liposomal-Annamycin is well tolerated, according to this research. Even though DOX's precise modes of action are complicated and still not fully understood, it is known that this anticancer medication inhibits topoisomerase and intercalates into DNA. To learn more about the cellular and molecular processes behind paclitaxel's effects in different medical diseases, more research is required.
Breast cancer is treated with tamoxifen. Nanotechnology research will soon bring about a significant transformation in cancer as well as in all other medical specialities.

REFERENCE

1. Naeem M, Khalil AAK, Li J, Nasir A, Khan A, et al. A review article of Nanotechnology, A Tool for Diagnostics and Treatment of Cancer. Bentham Science Publishers. 2021:1360–1376. doi:10.2174/1568026621666210701144124. Retrieved on 2023 Nov 25.

2. Dolati S, Ahmadi M, Baghbanzhadeh A, Asadi M, Fotouhi A, Aghebati-Maleki A. Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers. J Cell Physiol. 2019;1–11. doi:10.1002/jcp.29126. Retrieved on 2023 Nov 25.

3. Wantong S, Huang L, Anselmo AC. Nanotechnology intervention of the microbiome for cancer therapy. Springer Nature. 2019. Accessed on 2023 Nov 25.

4. Singh A, Singh VK, Singh MP, Chaturvedi VK. Cancer Nanotechnology: A New Revolution for Cancer Diagnosis and Therapy. Bentham Science Publishers. 2019;20:416-429. doi:10.2174/1389200219666180918111528. Retrieved on 2023 Nov 25.

5. Chen X, Deng L, Shen Z, Lau J, Tang W, Fan W. Emerging blood–brain-barrier-crossing nanotechnology for brain cancer theranostics. Chem Soc Rev. 2019. doi:10.1039/c8cs00805a. Retrieved on 2023 Nov 25.

6. Karikachery AR, Thipe VC, Srisrimal D, Mohandoss DKD, Khoobchandani M, Katti KK. New Approaches in Breast Cancer Therapy Through Green Nanotechnology and NanoAyurvedic Medicine – Pre-Clinical and Pilot Human Clinical Investigations. Int J Nanomedicin. 2020:181-197. doi:10.2147/UN.S219042. Retrieved on 2023 Nov 26.

7. Jov̇cevska I, Zottel A, Videtiʇc Paska A. Nanotechnology Meets Oncology: Nanomaterials in Brain Cancer Research, Diagnosis and Therapy. Materials (Basel). 2019. doi:10.3390/ma12101588. Retrieved on 2023 Nov 26.

8. Gupta G, Singh H, Kaur S, Dhanjal DS, Mehta M, Sharma P. Emerging trends in the novel drug delivery approaches for the treatment of lung cancer. Chem Biol Interact. 2019. doi:10.1016/j.cbi.2019.06.033. Retrieved on 2023 Nov 26.

9. Dana H, Gharagouzloo E, Grijalvo S, Eritja R, Logsdon CD, Mahmoodi Chalbatani G. Small interfering RNAs (siRNAs) in cancer therapy: a nano-based approach. J Nanosci Nanotechnol. 2019. doi:10.2147/JN.S200253. Retrieved on 2023 Nov 26.

10. Kesari KK, Kamal MA, Garg N, Ruokolainen J, Das BC, Kumar D, et al. Specific targeting cancer cells with nanoparticles and drug delivery in cancer therapy. Semin Cancer Biol. 2019. doi:10.1016/j.semcancer.2019.11.002. Retrieved on 2023 Nov 27.

11. Dong P, Hussein Y, Rakesh KP, Manukumar HM, Sumathi S, Karthik CS, et al. Innovative nano-carriers in anticancer drug delivery-a comprehensive review. Bioorg Chem. 2019. doi:10.1016/j.bioorg.2019.01.019. Retrieved on 2023 Nov 27.

12. Ferrari M, Wolfram J. Clinical Cancer Nanomedicine. Elsevier 2019. doi:S1748013218306388. Retrieved on 2023 Nov 28.

13. Barani M, Rahdar A, Bilal M, Mukhtar M. Nanomaterials for Diagnosis and Treatment of Brain Cancer. Chemosensors. 2020. doi:10.3390/chemosensors8040117. Retrieved on 2023 Nov 28.

14. Sanna V, Pala N, Sechi M. Targeted therapy using nanotechnology: focus on cancer. Int J Nanomedicine. 2014. doi:10.2147/UN.S36654. Retrieved on 2023 Nov 28.

15. Rao J, Nel AE, Lanza GM, Bradbury MS, Hartshorn CM. Nanotechnology Strategies To Advance Outcomes in Clinical Cancer Care. ACS Nano. 2018. doi:10.1021/acsnano.7b05108. Retrieved on 2023 Nov 28.

16. Santos MS, Oliveira PJ, Cardoso S, Correia S, Santos RX, Carvalho C. Doxorubicin: The Good, the Bad and the Ugly Effect. 2019. doi:10.2174/092986709788803312. Retrieved on 2023 Nov 29.

17. Dong Z, Yang R, Wang S, Zhang D. Paclitaxel: new uses for an old drug. Dove Medical Press. 2014. doi:10.2147/DDDT56801. Retrieved on 2023 Nov 29.

18. Al-Mosawi K, Al-Mosawe HAS, Al-Janabi AAHS. Tamoxifen: From Anti-cancer to Antifungal Drug. Int J Med Rev. 2019;6(3):88-91. doi:10.29252/ijmr060304. Retrieved on 2023 Nov 30.

19. Al-Janabi AAHS, Al-Mosawe HAS, Al-Mosawi K, et al. Tamoxifen: From Anti-cancer to Antifungal Drug. Microbiology, College of Medicine, University of Karbala. 2019 May 5 [Accepted 2019 Aug 28; Published online 2019 Sep 16].