Recent advances in nanoformulation-based delivery for cancer immunotherapy

Abstract

Cancer is one of the leading causes of mortality worldwide, and its treatment faces several challenges. Phytoconstituents derived from recently discovered medicinal plants through nanotechnology potentially target cancer cells via PI3K/Akt/mTOR pathways and exert their effects selectively through the generation of reactive oxygen species through β-catenin inhibition, DNA damage, and increasing caspase 3/9 and p53 expression. These nanocarriers act specifically against different cancer cell lines such as HT-29, MOLT-4 human leukemia cancer and MCF-7 cell lines SKOV-3, Caov-3, SW-626, HepG2, A-549, HeLa, and MCF-7. This review comprehensively elaborates on the cellular and molecular mechanisms, and therapeutic prospects of various plant-mediated nanoformulations to attain a revolutionary shift in cancer immunotherapy.

Article Highlights

Background & approaches for nanoformulations design

• Drug nanofabrication using the multidisciplinary field of nanotechnology may be a possible solution for the treatment of cancer.

• Medicinal plants as natural sources of anticancer compounds are the most suitable, safe, and cost-effective alternatives to traditional chemical drugs, and nanoencapsulation of plant bioactive compounds could effectively improve cancer treatment.

• The main approaches for the proper synthesis of nanoformulated drugs are top-down and bottom-up methods, considering the key features of particle size, shape, structure as well as particle size distribution.

Modes of delivery routes

• An efficient drug-delivery system is site-specific with minimum loss in blood circulation, improved bioavailability and biocompatibility and without harmful effects on noncancerous cells.

• The nanocarriers are capable of crossing diverse biological barriers and improve bioaccessability of anticancer drugs when administered orally.

• The transdermal, intravenous, and pulmonary administration of nanoparticles (NPs) avoid first-pass metabolism, reduce systemic toxicity, and improve bioavailability of drugs through passive and active targeting of cancerous tissues.

Plant-mediated nanoformulations for cancer therapy

• Natural antitumor agents are of great importance with more than 60% of cancer treatments using natural sources, focusing on green synthesis of NPs. Plants have been preferred for this purpose.

Hydrophilic & hydrophobic nature of NPs

• An important parameter for risk considerations of biological interactions of NPs is their relative hydrophobicity.

• Hydrophobic NPs attach to and interact with cell lipid bilayer membrane and exhibit enhanced uptake compared with hydrophilic NPs.

Clinical trials

• Many clinical and preclinical studies have proved the effectiveness of nanoformulated drugs, but unfortunately not many nanodrugs have received approval for clinical application. At present, ~16 anticancer nanodrugs have been approved by the US FDA, 75 are in clinical trials, and five are available in market.

Current challenges

• The main limitation to medical application of naturally synthesized NPs is their toxicity in tissues and determining how to obtain the ideal size and monodispersion of particles.

Future perspective

• Using properly regulated methods, adjustment of parameters during NP synthesis and co-delivery of combinative natural nanodrugs can improve cancer immunotherapy in the future.

Keywords: :

• anticancer
• apoptosis
• cell cycle
• cytotoxicity
• medicinal plants
• nanoparticles
• reactive oxygen species

Author contributions

SS Bokhari: conceptualization, validation, writing – original draft. T Ali: conceptualization, validation, data curation, project administration, writing – review & editing. M Naeem: validation, data curation, writing – review & editing. F Hussain: validation, project administration, supervision A Nasir: validation, visualization, writing – review & editing.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.