Variety of Nanoparticles for Treatment of Lung Cancer

Abstract on Transformable Liquid-Metal Nanomedicine

The nanotechnology has been developed to a greatest extent and is still developing a lot in the field of science. The use of nanoparticles that occur in the range of 1-100nm re being used in developing the material which can be utilised as the medicine, delivery of drugs and many other potential forms. The drug Doxorubicin has been attained from Streptomyces and has been used as the anti-cancer drug for a long time along with several different types of nanoparticle targeted delivery modes. The drug and its nanoparticle are prepared before releasing into the body by the help of the linker molecule and polymerization, that forms a drug loaded nanoparticle to increase the efficiency as well as the capacity of the nanoparticle for action against the cancer cell. There are variety of modes for delivery of the drug to its target location such as tumour-exosome, injectable Nanoparticles Generators, multivalent Porous Silicon Nanoparticle, Cell-Membrane derived, Indocyanine Green Nanoparticle, DNA Nanoplatform therapy and the Undecylenic Acid Conjugated nanoparticles are various modes of targeting the cancer cells. In addition to this the technology is still developing such as the platelet derived nanoparticles have been brought into places. There are several other future endeavours that have helped the human race to reach to the height of development which we never had.

Introduction to Transformable Liquid-Metal Nanomedicine

The nanotechnology is the science of dealing with the nanoparticles that are in the size range of 1 – 100 nanometres and they can be altered in their physical and chemical structure according to the needs (Kumar, Boruah, & Liang, 2011). The nanotechnology has been used for long term now and their paradigms have answered most of the problems the world used to face in every possible field of science. The use nanoparticles in the field of biology has paved the step toward the better treatment of diseases such as the Cancer, Hepatitis and many others. The therapeutic use of nanoparticles has been applied in treating the cancer, by providing the precision drug delivery system that will involve the use of drug linked with the nanoparticles to reach to the target cells. Biomimetics is the approach that has been recently applied in the field of nanomedicine in which the a biological structure is mimicked with the help of the nanoparticles and help in the targeting the drug delivery (Yong, Zhang, Bie, & al, 2019).

In handling some cancers, nanoparticles are functionally prepared with other ligands such as the antibodies, protein metabolites and other molecules that provide the precision and effective attacking rate of the molecule (Yong, Zhang, Bie, & al, 2019).

This review article is going to focus upon the use of various nanoparticle targeting platforms usually loaded up with the drug Doxorubicin in order to attack on the Lung cancer. These cancerous cells metastasize to other cells in the body as they are able to penetrate deeper into the cells and releasing the drug at the place affected. These drugs are loaded upon the nanoparticles which can be targeted by using different types of nanoparticles.

Anti – Cancer Drug Doxorubicin [DOX] in Lung Cancer

Doxorubicin is the anti-neoplastic drug is the anthracycline that is used in attacking on cancer cells at deeper levels. In Lung Cancer the chemotherapy drugs used that are Tyrosine kinase inhibitor, and do not attack the cells with as efficiently as this doxorubicin. This drug is highly efficient in attacking the cancer cells due to the fact that they are loaded upon the nanoparticles, which helps in target mediated therapy on the cancer cells. The doxorubicin for Lung cancer therapy is developed with the polyvinylpyrrolidone (PVP) and loaded upon the Gold Nanoparticles (AuNP) and is represented as DOX@PVP-AuNPs (Ramalingam , Varunkumar, Ravikumar , & Rajaram, 2018).

Doxorubicin has different types of approaches in regards of the action into the body. The dynamics of this drug in which they can either intercalate into the DNA and then cause the destruction of the DNA repair process mediated by the Topoisomerase – II, or it can also act upon damaging the cellular structures including membranes, DNA proteins by producing the free radicals into the cell (Thorn, 2011).

However, as in pharmacology it is said that everything is poison if its amount is not checked properly and the same thing occurs with the non-metabolised molecules of the drug Doxorubicin. Doxorubicin is the anthracycline compound that are conjugated upon the nanoparticle of 107nm size (Lu, 2015) that has the anti-neoplastic properties and it is helpful DOXol[1] and aglycones are the metabolites of the doxorubicin that may lead to the significant amount cardiac side effects in the body. These side effects cause multiple problems in the body when their level is higher to the level of their toxic dose. This calls from multiple disorders and most of them are of cardiovascular in nature. When these levels are not checked properly in the body this leads to the failure of the heart and many other diseases such as cardiomyopathy, cardiac arrest, heart attacks and many others (Licata, Saponiero, Mordente, & Minotti, 2000).

Modes of Targeting Cancer Cells

There are different modes of targeting a cancer cell and it requires the building of the nanoparticle which is attached with the ligand that acts as the molecule which will attack the cancer cells. These ligands are delivered at the site by the help of the nanoparticles designed for the purpose (Chou, Zagorovsky, & Chan , 2014). There are variety of Nanoparticles which are chosen on the basis of the location of the target and the type of therapeutic which has to be used in order to treat the cancer.

In order to create a drug that is ready for the targeted therapy in Cancer therapeutics, certain elements are required to be connected with the nanoparticles and the drug that helps during the mechanism of the drug action. This type of connecting link between the molecule and the nanoparticle is termed as the linker molecule and it helps in adjoining the two entities together in order to provide them stability in the body till the moiety reaches to the target area for its action (Xu, Zhang, & Mai, 2016). Other preparatory mode of delivering the compound in the body is through the help of polymerization of the either the drug molecule or of the nanoparticle as it can be beneficial in further increasing the stability of the molecule as well increases the capacity of the moiety to carry the amount of drug at the site of the target. The moiety can also be used to attach it with the cell membrane of the known cell type of the body so as to increase the availability of the drug in the deeper areas of the cancer affected region in the body.

The drug doxorubicin when loaded upon the nanoparticles is able to penetrate deep into the cancer cells and then target the cell at cellular level. It also acts upon the DNA of the cancer cell by which the ability of the cell to replicate into more cancerous cell is inhibited. This ability of the drug makes it most powerful drug as an anti-neoplastic molecule which has been researched more than any other drug.

The nanoparticles can also influence the action of the drug and affect its efficiency at the target site as they are required to reach to the deeper part of the cancer affected region. This can be achieved through the help of making the use of porous silicon based nanoparticles (Gu, Ruff, & Qin, 2012).

The cancer of lungs can be treated in many ways such as surgery, chemotherapy but there is always the chance of its relapse in the body due to actively dividing cells of the region. This called for the need of the new technology in the science that can deal with the problem at the deeper level of disease. The root cause of the cancer is the inability of the cells to stop from dividing uncontrollably in the cells.

The Cancer treatment is being researched a lot with the help of the nanotechnology as it makes the potential candidate for targeting the drugs at the site of the affected part of the body. In order to check the efficacy of the therapeutic effect by observing its enhanced, permeability and retention effect in the body (EPR[2]) (Maeda , Nakamura H, & Fang, 2013).

Sometimes the ligand not just acts as the therapeutic molecule for the cancer but also helps in imaging (Liong, et al., 2008) the site affected due to the cancer as there are many dyes such as the Rhodamine B which if injected into the body without the nanoparticles does not reveals the fluorescent effect. However, with the help of the BSA[3] (Yu, Yu, Zhang, Hong, & Xiong, 2014) conjugated Rhodamine B nanoprobe visualises the area that has the tumour (Maeda , Nakamura H, & Fang, 2013).

The various modes of targeting the cancer cells can be found in the Table 1 - Different modes of delivery for the Nanoparticles in Targeted Cancer Therapy that has all the relevant information about the ligands as well as the type of the nanoparticle used for the purpose of research in nanomedicine. These targeted therapies and their participant molecules have also been discussed in brief in order to plot the idea of their working, action mechanism in the body and their preferred nanoparticles in that category.

  1. Tumour – Exosome Nanoparticle - The exosomes are the extracellular vesicles which when conjugated with the Nanoparticles helps in increasing the drug carrying capacity of the molecule and are thus highly effective in killing the cancer cells (Batrakova & Kim, 2015). The nanoparticles used for this purpose are Porous Silicon Nanoparticles sheathed by the exosome and conjugated with the drug such as the Doxorubicin are termed as DOX@EPSiNPs which are very active during the accumulation into the tumour parenchyma(Yong, Zhang, Bie, & al, 2019).
  2. Injectable Nanoparticle generator (iNPG) – The iNPGs[4] are the nanoparticles that are associated with the drug as the conjugated part and contains the linker molecule which is pH sensitive and helps in keeping the drug in its polymer form. The drug used in this is the Polymeric form of Doxorubicin and it is brought in polymeric form by the help of L-Glutamic Acid and a pH sensitive linker. These nanoparticles open themselves intratumorally and helps in targeting the cells of cancer with the ample amount of the drug to kill the cells(Xu, Zhang, & Mai, 2016).
  3. Multivalent Porous Silicon Nanoparticles – The multivalent nanoparticles are the molecules that are prepared for increasing the activity of the CD40 antibody in the body. They are designed and prepared by the help of the Avidin protein which later allows for the attachment of the antibody FGK45 to the structure creating the FGK-LPSiNPs that are FGK45 conjugated Luminescent Porous Silicon Nanoparticles. It acts upon the antigen presenting cells (APCs[5]) of the body (Gu, Ruff, & Qin, 2012).
  4. Cell – Membrane derived Nanoparticles – These structures are designed specifically to combat the attack from the natural immune cells of the body as they are prepared by the help of the cellular membrane of the cells from the body such as the RBCs. After attaching the nanoparticle core into the cell membrane of the RBC, these cells are then inserted into the body. They can be used as part of the systemic circulation, can be used to target specific cells by preparing the cell membrane with appropriate molecule and by bringing in the multi drug therapy in it (Luk & Zhang, 2015).
  5. Indocyanine Green Nanoparticle – The Indocyanine Green dye is a biomimetic particle that is loaded upon the cancer cell membrane Nanoparticle. The core of this structure contains the polymeric form of the Indocyanine Green nanoparticles which help in reaching to the target cells. This can be used in conjugation with the drug to attack on the cancer cells as well as in helping to image the area of the affected region due to the cancer. This nanoparticle hordes the NIR[6], FL/PA[7] properties that helps in analysing the structure with better accuracy (Chen, Zhao, & Luo, 2016).
  6. DNA Nanoplatform Therapy – The DNA nanoplatform therapy is prepared with the help of the versatile DNA structure that is capable of delivering small interfering RNAs at the site. The nanoplatform is prepared by the help of the two small hairpin RNA transcripts, chemo drug (Doxorubicin conjugation), an anti-apoptotic gene and they are arranged in the pre-loaded DNA origami. This helps in targeting the cells directly and causing the inhibition of the tumour growth without causing any visible toxicity of the drug (Liu, Song, Liu, & Zhao, 2018).
  7. Undecylenic Acid Conjugated Nanoparticle – The Undecylenic Acid nanoparticle are helpful in targeting the cells of the tumour at the deeper levels. The UA-LPSiNPs[8] are responsible for the macropinocytosis, clathrin mediated endocytosis and they co-localize themselves with the Golgi apparatus as well as with the lysosomes. They can also be conjugated with the DOX[9] drug in order to affect the nearby cancer cells by penetrating deep into their cellular platform (Yong, 2016).

Delivery Mode

Nanoparticle

Ligand

Tumor – Exosome Nanoparticle

Porous Silicon Nanoparticles (PSiNPs)

Exosome

Injectable Nanoparticle Generator (iNPG)

Injectable Nanoparticles

Polymeric Doxorubicin (pDOX)

Multivalent Porous Silicon Nanoparticles

Luminescent Porous Silicon Nanoparticles (LPSiNPs)

Antibody FGK45

Cell Membrane derived Nanoparticles

Nanoparticle Core

Cell Membrane (RBCs)

Indocyanine Green Nanoparticle

Cell Membrane coated Nanoparticle

Indocyanine Green (ICG polymeric core)

DNA Nanoplatform Therapy

DNA Nanostructure

Small hairpin RNA (shRNA) and Doxorubicin

Undecylenic Acid Conjugated Nanoparticle

Luminescent Porous Silicon Nanoparticles (LPSiNPs)

Undecylenic Acid

Table 1 - Different modes of delivery for the Nanoparticles in Targeted Cancer Therapy

Future Endeavours and Advancements

The scope of nanomedicine is widening with every new researcher is pacing towards the development of new nanoparticle technology and its flow of development is always uphill in terms of development one should not lose focus and hope from what’s new is going to come and change their lives. There are many other advancements that are not defined in detail in this review such as the treatment of the immune thrombocytopenia antibody camouflaged as the platelet are used. In this study the platelets were used to fill them with nanoparticles and then they were placed in the body to target the cells of the cancer and it is yet to be studied in detail (Wei, 2016).

Another biomimetic study for the treatment of the breast cancer has been going on that involves the use of the Paclitaxel-loaded Polymeric Nanoparticles (Colombo, 1999) that are highly specific in targeting the cancer cells, metastases as well as inhibiting the growth of the tumour from growing. These cells are the cancer cell-membrane bound with the nanoparticles and reveals the superior form of interactions with their ancestral cells of tumours. PPNs[10] have been of great use to the treatment of the 4T1 Breast cancer cells as well as the inhibition of the Lung cancer metastases (Sun , 2016).

Conclusions on Transformable Liquid-Metal Nanomedicine

The field of Bio-nanotechnology has been developing from many years now and is the light of the future world where every treatment, medicine will be developed on the grounds of the nanomedicine. The development of nanotechnology is beyond medicine and chemistry it has been used in making materials that are cheaper and durable to eternity.

Just as Nanotechnology has widened its horizons with proper research the aspect of its applications in the field of medicine do not just stand at the treatment of the infectious as well as the non-infectious diseases, it will soon be taken in building the prosthetic arms that will feel exactly the same as the old one.

There are variety of modes by which the nanoparticles can be used to get loaded with the drug or the dye which is to be sent into the body and visualise the area affected by the cancerous cells in the body.

In many aspects Doxorubicin [DOX] has been used as the drug that has cleared many gateways for solutions of the problems that are arising during the treatment of Lung Cancer problems. The drug doxorubicin has many potentials uses and they have also helped in the treatment of the cancer as well as enhancing the visualising of the area that is affected by the cancer. This drug can be potentially loaded upon variety of the nanoparticles that helped in the deeper penetration of the drugs directly impacting at the site of the cancer affected portions of the cell.

References for Transformable Liquid-Metal Nanomedicine

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