Review Article

Nanobiotechnology in Drug Delivery: How Nanoparticles are Revolutionizing Targeted Cancer Treatment

Vaibhav Gupta^1* and Ragini Rai²

¹School of Pharmaceutical Education and Research (SPER), Jamia Hamdard University, New Delhi, 110062, India

²School Of Pharmacy (SOP), Bharat Institute of Technology, Meerut, Uttar Pradesh, 250103, India

Submission: September 19, 2024; Published: October 08, 2024

*Corresponding author: Vaibhav Gupta, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard University, New Delhi, 110062, India. Email: vaibhavggn@yahoo.com

How to cite this article: Vaibhav G, Ragini R. Nanobiotechnology in Drug Delivery: How Nanoparticles are Revolutionizing Targeted Cancer Treatment. Adv Biotech & Micro. 2024; 18(3):555988.DOI:10.19080/AIBM.2024.18.555988

Abstract

Cancer treatment has traditionally relied on non-specific approaches such as chemotherapy and radiation, which often result in severe side effects and limited efficacy due to the inability to precisely target cancer cells. Recent advancements in nanobiotechnology have introduced nanoparticles as powerful tools for targeted drug delivery, offering a significant breakthrough in cancer therapy. Nanoparticles, such as liposomes, polymeric nanoparticles, and metal-based nanoparticles, are engineered to deliver drugs directly to tumor cells, minimizing toxicity to healthy tissues and enhancing therapeutic outcomes. This review discusses the various types of nanoparticles used in cancer drug delivery, focusing on their mechanisms of targeting cancer cells, including passive targeting via the Enhanced Permeability and Retention (EPR) effect and active targeting through surface modifications that recognize specific cancer cell receptors. Additionally, we explore the advantages of nanoparticle-based drug delivery systems, such as improved drug solubility, reduced systemic toxicity, and overcoming multidrug resistance, all of which contribute to a more personalized and efficient approach to cancer treatment. The review also highlights recent clinical applications and ongoing trials involving nanoparticle formulations, emphasizing their role in revolutionizing oncology. Despite the promising developments, challenges such as biological barriers, safety concerns, and regulatory issues still persist. This article concludes by outlining future directions and the potential for nanobiotechnology to transform cancer therapies, paving the way for more targeted and less invasive treatment options.

Keywords: Nanoparticles; Cancer Treatment; Targeted Drug Delivery; Liposomes; Polymeric Nanoparticles; Tumor Targeting; Nanomedicin

Abbreviations: EPR: Enhanced Permeability and Retention; PTT: Photothermal Therapy; MRI: Magnetic Hyperthermia; MDR: Multidrug Resistance: RES: Reticuloendothelial System

Introduction

Overview of nanobiotechnology in drug delivery

Nanobiotechnology, the convergence of nanotechnology and biotechnology, has revolutionized modern drug delivery systems. This interdisciplinary field involves the manipulation of matter at the nanoscale (1-100nm) to develop novel therapeutic and diagnostic tools. In the context of drug delivery, nanobiotechnology enables the creation of highly precise, targeted systems that can overcome many limitations of conventional treatment methods. [1-4]

The concept of targeted drug delivery is particularly crucial in cancer treatment. It involves directing therapeutic agents specifically to cancer cells while minimizing exposure to healthy tissues. This approach holds immense potential for improving treatment outcomes and patient quality of life. [5-8]

Challenges in traditional cancer treatment

Despite significant advancements, traditional cancer treatments such as chemotherapy, radiotherapy, and surgery continue to face substantial challenges. These include:

• Severe side effects due to non-specific targeting of healthy cells

• Development of drug resistance in cancer cells

• Limited ability to penetrate solid tumors effectively

• Poor solubility and bioavailability of many anticancer drugs

These limitations often result in suboptimal therapeutic outcomes and diminished quality of life for patients undergoing treatment. [9-11]

Revolution of nanoparticles

Nanoparticles have emerged as a promising solution to overcome the challenges associated with traditional cancer treatments. By leveraging their unique properties, nanoparticles offer several advantages:

• Enhanced drug solubility and stability

• Improved pharmacokinetics and biodistribution

• Targeted delivery to tumor sites

• Controlled and sustained drug release

• Ability to overcome biological barriers

These characteristics enable nanoparticle-based therapies to potentially improve treatment efficiency while minimizing damage to healthy tissues. [12-16]

Types of nanoparticles used in cancer drug delivery

Liposomes

Liposomes are spherical vesicles composed of phospholipid bilayers that encapsulate an aqueous core. Their structure mimics biological membranes, conferring high biocompatibility and versatility in drug delivery.[17]

Advantages:

• High biocompatibility and biodegradability

• Ability to encapsulate both hydrophilic and hydrophobic drugs

• Long circulation time when PEGylated

• Reduced toxicity of encapsulated drugs

Example: Doxil®, a PEGylated liposomal formulation of doxorubicin, was the first FDA-approved nano-drug for cancer treatment. It demonstrates improved pharmacokinetics and reduced cardiotoxicity compared to free doxorubicin.[18]

Polymeric nanoparticles

Polymeric nanoparticles are solid colloidal particles made from biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA) or PEGylated polymers. [19-21]

Key features:

• Controlled and sustained drug release

• High stability and drug loading capacity

• Customizable surface properties for targeted delivery

FDA-approved formulations: Abraxane®, an albumin-bound paclitaxel nanoparticle, has shown improved efficacy and reduced toxicity in treating various cancers.[22]

Metal-based nanoparticles

Metal-based nanoparticles, particularly gold and iron oxide nanoparticles, have gained attention for their unique properties in cancer therapy.[23]

Applications:

• Gold nanoparticles: Photothermal therapy (PTT) and radio sensitization

• Iron oxide nanoparticles: Magnetic hyperthermia and MRI contrast enhancement

These nanoparticles can be functionalized for targeted delivery and offer theranostic capabilities, combining therapy and diagnostics. [23-26]

Quantum dots

Quantum dots are semiconductor nanocrystals with unique optical and electronic properties. While primarily used for imaging, they also show promise in drug delivery. [27,28]

Advantages:

• Exceptional brightness and photostability for imaging

• Size-tunable emission spectra

• Potential for simultaneous imaging and drug delivery (theranostics)

However, concerns about potential toxicity have limited their clinical translation thus far.

Mechanisms of targeted drug delivery using nanoparticles

Enhanced permeability and retention (EPR) effect

The EPR effect is a passive targeting mechanism that exploits the unique characteristics of tumor vasculature. Rapidly growing tumors develop leaky blood vessels with wide fenestrations, allowing nanoparticles to accumulate preferentially in tumor tissues. [29,30].

Key points:

• Nanoparticles of appropriate size (typically 10-200nm) can extravasate through leaky tumor vessels

• Poor lymphatic drainage in tumors leads to retention of nanoparticles

• EPR effect enables passive accumulation of nanoparticles in tumors, enhancing drug delivery efficiency [29,30]

Active Targeting

Active targeting involves functionalizing nanoparticles with ligands that specifically bind to receptors overexpressed on cancer cells. [31,32]

Strategies:

• Antibody conjugation (e.g., anti-HER2 for breast cancer)

• Peptide functionalization (e.g., RGD peptides for targeting angiogenic blood vessels)

• Small molecule ligands (e.g., folate for targeting folate receptors)

Active targeting can enhance cellular uptake and intracellular drug delivery, potentially improving therapeutic efficacy.[31]

Stimuli-responsive Nanoparticles

Stimuli-responsive nanoparticles are designed to release their drug payload in response to specific environmental cues present in the tumor microenvironment.[33]

Stimuli used for triggered release:

• pH (exploiting the acidic tumor microenvironment)

• Temperature (using external heat application)

• Enzymes (e.g., matrix metalloproteinases overexpressed in tumors)

• Redox potential (higher glutathione concentration in tumor cells)

These “smart” nanoparticles offer precise spatial and temporal control over drug release, potentially enhancing therapeutic index. [34,35]

Advantages of nanoparticle-based drug delivery in cancer treatment

Increased drug solubility and stability

Many anticancer drugs are hydrophobic and poorly soluble in aqueous media, limiting their bioavailability. Nanoparticles can improve drug solubility through various mechanisms:

• Encapsulation within hydrophobic cores (e.g., polymeric micelles)

• Formation of nanoemulsions

• Complexation with cyclodextrins or other solubilizing agents

This enhanced solubility can lead to improved drug absorption and bioavailability. [36-38]

Reduced systemic toxicity

By enabling targeted delivery to tumor sites, nanoparticles can significantly reduce systemic exposure to cytotoxic drugs. This targeted approach helps mitigate common side effects associated with chemotherapy, such as:

• Nausea and vomiting

• Hair loss

• Myelosuppression

• Cardiotoxicity

For example, liposomal doxorubicin formulations have demonstrated reduced cardiotoxicity compared to free doxorubicin while maintaining anticancer efficacy. [39,40]

Overcoming drug resistance

Multidrug resistance (MDR) is a major challenge in cancer therapy. Nanoparticles can help overcome MDR through various mechanisms:

• Bypassing efflux pumps (e.g., P-glycoprotein) responsible for drug efflux

• Co-delivery of chemosensitizers with anticancer drugs

• Targeted delivery of siRNA to silence MDR-associated genes

These strategies can potentially resensitize resistant tumors to chemotherapy. [41,42]

Personalized medicine

Nanoparticles offer unique opportunities for personalized cancer therapy:

• Theranostic nanoparticles combining imaging and therapeutic functions

• Tailored nanoformulations based on individual patient tumor characteristics

• Real-time monitoring of treatment response using nanoparticle-based imaging agents

This personalized approach has the potential to optimize treatment outcomes and minimize unnecessary side effects. [43- 47].

Clinical applications and recent advances

FDA-Approved nanoparticle drugs for cancer

Several nanoparticle-based cancer therapies have received FDA approval and are in clinical use:

• Doxil® (pegylated liposomal doxorubicin)

• Abraxane® (nab-paclitaxel)

• Onivyde® (liposomal irinotecan)

• Marqibo® (vincristine sulfate liposome injection)

• These approved nanoformulations have demonstrated improved efficacy and/or reduced toxicity compared to their conventional counterparts [Citation needed].

Clinical trials of nanoparticles in cancer therapy

Numerous clinical trials are currently evaluating novel nanoparticle-based cancer therapies. Some notable examples include:

• CRLX101: A nanoparticle-drug conjugate of camptothecin (Phase II for various solid tumors) [48,49]

• MM-398: A nanoliposomal formulation of irinotecan (Phase III for pancreatic cancer) [50]

• BIND-014: A PSMA-targeted docetaxel nanoparticle (Phase II for prostate cancer) [51]

These trials are assessing safety, efficacy, and potential advantages over conventional therapies.

Breakthroughs in Nanoparticle Research

Recent advancements in nanoparticle research show promise for future cancer therapies:

• Development of multi-functional nanoparticles combining therapy and diagnostics

• Novel targeting strategies, such as biomimetic nanoparticles

• Integration of nanoparticles with immunotherapy approaches

• Exploration of RNA-based nanoparticles for gene therapy

These innovative approaches are paving the way for more effective and personalized cancer treatments. [52-54]

Challenges and future directions

Biological barriers

Despite their promise, nanoparticles face several biological barriers that can hinder their efficacy:

• Opsonization and clearance by the reticuloendothelial system (RES)

• Limited penetration into solid tumors due to high interstitial fluid pressure

• Heterogeneous distribution within tumors

Ongoing research focuses on overcoming these barriers through innovative nanoparticle designs and delivery strategies. [52-54]

Toxicity and safety concerns

Long-term safety and potential toxicity of certain nanoparticles remain significant concerns:

• Accumulation of non-biodegradable nanoparticles in organs

• Potential immunogenicity of nanoparticle components

• Toxicity associated with specific materials (e.g., quantum dots containing heavy metals)

Rigorous safety assessments and long-term follow-up studies are crucial to address these concerns. [54-57]

Regulatory hurdles

The complex nature of nanoparticle-based therapies presents unique regulatory challenges:

• Establishing appropriate characterization methods for nano-formulations

• Defining safety and efficacy standards specific to nanomedicines

• Harmonizing regulatory guidelines across different regions

Collaboration between regulatory agencies, researchers, and industry is essential to streamline the approval process for nanomedicines. [58,59]

Future prospects

The future of nanobiotechnology in cancer therapy holds immense promise:

• Integration of artificial intelligence for nanoparticle design and optimization

• Development of “smart” nanoparticles responsive to multiple stimuli

• Combination therapies utilizing nanoparticles (e.g., chemo-immunotherapy)

• Personalized nanoparticle formulations based on individual patient characteristics

These advancements have the potential to significantly improve cancer treatment outcomes and patient quality of life. (Figure 1).

Conclusion

Nanoparticles have emerged as powerful tools in the fight against cancer, offering unprecedented opportunities for targeted drug delivery and personalized medicine. By leveraging their unique properties, nanoparticle-based therapies can potentially overcome many limitations of traditional cancer treatments, leading to improved efficacy and reduced side effects. While significant progress has been made, with several nanoparticle-based drugs already in clinical use, numerous challenges remain. Ongoing research efforts focus on addressing these challenges, from ovesrcoming biological barriers to ensuring long-term safety and navigating complex regulatory landscapes.

As we continue to unlock the full potential of nanobiotechnology in oncology, the future of cancer treatment looks increasingly promising. The integration of advanced nanoparticle designs with cutting-edge technologies like artificial intelligence and personalized medicine approaches holds the potential to revolutionize cancer therapy, offering new hope for patisents worldwide. The field of nanobiotechnology in cancer treatment is rapidly evolving, and continued research, collaboration, and innovation will be crucial in translating these promising technologies into clinical reality. As we move forward, the synergy between nanotechnology and biotechnology promises to usher in a new era of more effective, precise, and personalized cancer therapies.

Acknowledgements

The authors are highly grateful to Jamia Hamdard, New Delhi and Bharat Institute of Technology, Meerut, Uttar Pradesh.

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