Bio-Inspired Nanomedicine An Emerging Trend For Drug Targeting Into Cancer Cells

Introduction

The mortality rate increases day-to-day due to most vulnerable disease cancer universally and current therapeutic mitigation bears high levels of diversity and complexity in therapeutic regime. The systemic application of chemotherapeutic agents often accompanied with serious side and adverse effects along with normal cell toxicity. The chemotherapy is often associated with poor selectivity; lack of uniform biodistribution, inefficient access of drug to tumor site along with multidrug resistance. Despite this chemotherapy in cancer patient assorted with severe side effect, variation in drug plasma profile, dose dumping, and patient incompliance. Due to considerable interest and growing scope of nanotechnology, a tremendous breakthrough has come in search of cancer disease, their origin and development, led to the better treatment and diagnosis [1, 2].

Further, development of advanced drug delivery based on nanotechnology had great impact on the improving cancer therapy. The chemotherapeutic delivery using nanocarrier ameliorates the pharmacological features of conventional anti-cancer agents. The receptor based novel drug delivery is the new concept of chemotherapeutic targeting for potential access of therapeutics to tumor site using functionalised nanocarrier. These carriers efficiently discharge nanodrug to the target site in a controlled way. The nano-scale delivery using carrier system could reach to no accessible cell structures thus leads to the localised disposition of drug resulting higher therapeutic concentration in the cells and minimise the drug adverse effect [3-6].    

The bio-inspired drug delivery system based on nanocarrier has a point of attraction that brought drastic change in the therapeutic approach in cancer treatment and diagnosis. The bio-inspired particle, novel particle based therapeutic replica has bio-similar features with biological systems. These particles interact with cellular elements by imitating the to and fro movements of cells within the body and thereby potentiates pharmacological action of therapeutics.

These particles designed in such a way that mimic the cellular integrity of biological system, such as cell surface, membrane fluidity, three dimensional structure of protein as well as the chemical composition of the particles. Bio-inspired therapeutic system offered better platform for drug delivery with respect to specific selectivity, drug targeting and potentiates their clinical utility compared to conventional drug delivery. Moreover, these nanocarriers are biodegradable, biocompatible and capable of discharging multiple payloads for site specific delivery [7-10].    

Bio-inspired nanocarriers have demonstrated a better ability than conventional therapeutics to carry drugs towards specific tissues, increasing their potentials in clinical applications. Overall, biologically derived nanocarriers are intrinsically biodegradable and are capable of targeting diverse drug payloads for delivery at specific sites [11].  

1. Bio-inspired therapeutic approach in cancer therapy

1.1. Microbes-inspired therapeutic delivery:

The concept of use bacteria as anticancer therapy was observed ten decades ago by W. Colley in United States post notification of in a patient suffering from neck cancer got recovered being infected with erysipelas. Bacterial cell could able to penetrate deeper into the tumor tissue in hypoxic and necrotic region. It also provided important information regarding the cancer states, therapeutic efficacy by external detection [12, 13].

In this drug delivery, bacteria are genetically engineered with a drug release switch that has controlled over simultaneous growth of bacteria and medicament release. For this purpose a contemporised lysis circuit was developed and evaluated. Moreover, feasibility of this circuit tested in a tumor microenvironment for determining their efficacy using the combination of SLC-3 bacteria with 5-fluorouracil.

For instances genetically engineered bacterial ghost lack genetic material produced by controlled expression of the cloned lysis gene E from bacteriophage species. Based on this carrier, Doxorubicin delivered to human colorectal cells has shown two fold improvements in anti-proliferative and cytotoxicity activity [14].

Microbot therapeutic delivery

The nanoparticles could be conjugated to bacteria for simultaneous delivery of nanoparticles carrying therapeutic cargos into cells through Microbot technique. This is genetically unmodified bacteria and has advantage over invasive delivery of bacteria into cells. The microbot carrying therapeutic payload by nanoparticle conjugation has great potential to colonize in the hypoxic region of tumor. Many types of bacteria are used for this purpose for example; Listeria Monocytogenes, and S. Typhimurium. The genetically unmodified bacteria were conjugated

with nanoparticles loaded with plasmid DNA via biotin–streptavidin interactions. When the bacteria successfully enters the cell; the nanoparticles are released, resulting in transcription and translation of the target proteins [15].

Virus-inspire therapeutic delivery

Virus is a nano-scale highly infectious particle comprised of nucleic acid molecules inside protein core. It has been widely explored as nano-vehicle nanomedicine targeting due to their ability to transfer RNA, DNA into host cells for replication. It was found that the drug loaded nanoparticle conjugated with capsid part of adenovirus, retrovirus for specific tumor cells targeting. Virus like particle is a self assembled spherical capsid made them devoid of genetic material and non-infectious and capable of delivering vast number of cargos into tumor cells.

C. E. Ashley et al., fabricated virus like particle (derived from bacteriophase) conjugated with paclitaxel for delivery in human hepatocellular carcinoma and observed 10-fold higher anti-cancer potential human hepatocellular carcinoma and author concluded that virus like particle could be used for cell specific deliver in tumor [16].

RBC inspired therapeutic delivery

Structurally it is oval biconcave disc, flexible with average diameter upto 8 micron. RBC shows high degree of biocompatibility, and complete biodegradability and no toxic affect in vivo. It acts as active transporter, long circulatory half-life (40 days in mice and 120 days in human) offer high drug encapsulation feature, and abundant surface area for modification  

Platelets inspired therapeutic delivery

It is an important component of blood and has significant role in physiological and pathological process likewise hemostasis as well as thrombosis by forming plug that seal damaged vessels and arrest bleeding and thus main the integrity of blood circulation. Recently, it has been observed that it has natural affinity for tumor cells in blood circulation draws considerable attention.

The platelet membrane coated core shell nanocarrier was fabricated for sequential and site- specific targeting, of tumor necrosis factor related apoptosis inducing ligand and anti-cancer drug. The decorated nanocarrier comprised of anticancer drug loaded nanogel surrounded by platelet membrane surface available for decoration with active ligand [17].

Cell organelle inspired therapeutic delivery

Recently, it has been pointed out that certain types of cancer cell membrane can be employed as cargos in active targeting approach. For example, indocyanine green loaded poly(lactic-co-glycolic acid) NP coated with cancer cell membrane was developed to synchronously identify and combat tumors. The result suggested that homogeneous targeting effect at cellular level and deeper penetration. Therefore, it could be considered as excellent platform homogeneous targeting, and image guided photothermal therapy [18].

Exosomes: It is cell-derived vesicle abundantly available in biological fluid. They are amphiphilic, with centre point composed of hydrophilic head and encircle by a bi-layer lipid membrane made of saturated phospholipids, and thus constitute stable exosome structure. Some work reported the exosomal delivery of anti-cancer agent, and siRNA.

Lipid based drug delivery

Solid lipid nanoparticles composed of solid lipid cores adhered to a surfactant to solubilise lipophilic drugs in aqueous colloidal dispersion for site-specific drug delivery. A pH responsive solid lipid nanoparticle was developed intended to deliver doxorubicin on human breast cancer cell resulted in superior anti-proliferative effect in MDR cancer cells [19-20].

Albumin bio-macromolecular based drug delivery of paclitaxel had a 4-fold increase in the cellular uptake of endothelial cells as compared to clinical formulation [21]. The Nanoscale structure of DNA molecule have large number of desirable characteristics meant for targeted drug delivery, such as bio-stability and biocompatibility within cells, and high cellular uptake, ideal platform for anticancer therapy [22].

Conclusion

Bio-inspired therapeutic system originates from biological sources for the treatment and mitigation of cancers are becoming a topic of discussion and an emerging trend for the scientist working in this arena. Owing to the unique characteristics and desired properties of long circulation in biological fluid and selective cellular internalisation in vivo has attracted the attention from scientist and industry in the recent years.

References

1. D. Hanahan and R. A. Weinberg, Hallmarks of cancer: The next generation, Cell, 2011, 144, 646–674.

2. L. Rao, et al., Red Blood Cell Membrane as a Biomimetic Nanocoating for Prolonged Circulation Time and Reduced Accelerated Blood Clearance, Small, 2015, 11, 36–46.

3. Md. Habban Akhter, Saima Amin. Nanocarriers in advanced drug targeting: Setting novel paradigm in cancer therapeutics. Artificial Cells, Nanomedicine, and Biotechnology. 2017; 46(5):873-884.

4. Md. Habban Akhter, Saima Amin. An investigative approach to the treatment modalities of squamous cell carcinoma. 2017. Curr drug deliv. 2017; 14:597-612.    

5. Md. Habban Akhter, Javed Ahsan. Advancement in nanotheranostics for effective skin cancer therapy: state of the art. Current Nanomedicine. 2018; 8:1-13.    

6. Md. Habban Akhter, Javed Ahmad. Epidermal growth factor based active targeting: A paradigm shift towards advance tumor therapy. Artificial Cells, Nanomedicine, and Biotechnology.2018:46(2);1-11.

7. Md. Habban Akhter. Nanotherapeutic Intervention in Cancer Disease. e-newsletter, November, 2017.

8. Md. Habban Akhter. Smart Nano-enabled drug career for combating tumor growth and progress. Pharma Focus Asia, September, 2018.

9. Md. Habban Akhter. Ligand Decorated Theranostic Nanomedicines: A novel therapeutic approach against tumor targeting. Pharma Focus Asia e-Newsletter, June 2019.

10. Md. Habban Akhter. Porous metal organic nanocomposite structure: An emerging nanocarrier for application in Pharmaceutical and Biomedical Sciences. Acta Sci Pharm Sci. Scientific Pharmaceutical Sciences 2018;2(12): 68-69.

11. J. Yoo, D. J. Irvine, D. E. Discher and S. Mitragotri, Bioinspired, bioengineered and biomimetic drug delivery carriers, Nat. Publ. Gr., 2011, 10, 521–535.

12. S. Liu, et al., Tumor-targeting bacterial therapy: A potential treatment for oral cancer, Oncol. Lett., 2014, 8, 2359–2366.

13. Habban Akhter, Nitin saigal, Sanjula baboota, Shah Faisal, Javed Ali.  A two pulse drug delivery system for amoxicilin: an attempt to counter the scourge of bacterial resistance against antibiotics. Acta Pharm.2011; 61:313–322.

14. S. Paukner, et al., Bacterial ghosts as a novel advanced targeting system for drug and DNA delivery, Expert Opin. Drug Delivery, 2006, 1, 11–22.

15. G. Dietrich, Bioengineering: Bacteria give nanoparticles a ride, Nat. Nanotechnol., 2007, 2, 394–395.

16. C. E. Ashley, et al., Cell-Specific Delivery of Diverse Cargos by Bacteriophage MS2 Virus-like Particles, ACS Nano, 2011, 7, 5729–5745.

17. Q. Hu, et al., Anticancer Platelet-Mimicking Nanovehicles, Adv. Mater., 2015, 27, 7043–7050.

18. Z. Chen, et al., Cancer Cell Membrane-Biomimetic Nanoparticles for Homologous-Targeting Dual-Modal Imaging and Photothermal Therapy, ACS Nano, 2016, 10, 10049–10057.

19. Hena Kausar, Mohd. Mujeeb, Md. Habban Akhter. Optimization of ethosomes for topical Thymoquinone delivery for the treatment of skin acne Journal of Drug Deliv Sci and Technol. 2019; 49:177–187.

20. Md. Habban Akhter, Ahmad A, Ali J, Mohan G. Formulation and Development of CoQ10 loaded s-SNEDDS for Enhancement of Oral Bioavailability. J Pharm Innov. 2014; (9):121-131.

21. W. J. Gradishar, Albumin-bound paclitaxel: a next-generation taxane, Expert Opin. Pharmacother, 2006, 7, 1041–1053.

22. W. Sun, et al., Transformable DNA nanocarriers for plasma membrane targeted delivery of cytokine, Biomaterials, 2016, 96, 1–10.