3.2 Berbrine:

Mechanism of Action of Berberine: Berberine exhibits multiple effects on cancer cells through various mechanisms:

a) Cell Proliferation: Berberine reduces cancer cell proliferation by binding to RXRα, which suppresses β-catenin function and upregulates miR-214-3p while decreasing SCT levels.

b) Autophagy Promotion: Berberine activates autophagy by inhibiting the PI3K/Akt/mTOR pathway and enhancing LC3B-II levels. It also induces autophagy via the JNK/Beclin1 pathway³.

3.3 Paclitaxel:

Mechanism action of Paclitaxel: Paclitaxel selectively binds to β-tubulin and promotes the polymerization and assembly of tubulin, which depletes intracellular tubulin, prevents spindle formation, leads to mitotic arrest in G2/M phase, terminates cell division and ultimately leads to cancer cell death⁴.

3.4 Quercetin:

Mechanism action of Quercetin:

a) Cell signaling: Quercetin can modulate the PI3K/Akt/mTOR, Wnt/β-catenin, and MAPK/ERK1/2 pathways⁵.

b) Metastasis: Quercetin can inhibit metastasis by reducing VEGF secretion and MMP levels.

c) JAK/STAT signaling pathway regulation: Quercetin can inhibit IL-6-induced glioblastoma cell growth and migration by regulating the STAT3 signaling pathway⁶.

3.5 Combrtastatin A-4:

Mechanism action of combrtastatin A-4: Combretastatin A-4 (CA-4) is a natural product that works in a number of ways to inhibit cancer cells and tumors:

Tumor blood flow disruption: CA-4 can disrupt tumor blood flow at a nontoxic dose, starving tumor cells of oxygen and nutrients and leading to their death.

a) Apoptosis: CA-4 can induce apoptosis in tumor cells.

b) Anti-angiogenic: CA-4 can inhibit angiogenesis, which is the process by which tumors form new blood vessels.

c) Antimetastasis: CA-4 can inhibit metastasis, which is the process by which tumors spread.

d) Antimigration: CA-4 can inhibit migration, which is the process by which tumors move⁷

3.6 Camptothecin:

Mechanism action of Campothecin:

a) S-phase-specific killing : CPT kills cells during S-phase by causing replication forks to collide with the topoisomerase I cleavable complex.

b) Activation of HR-mediated DSB repair : CPT-induced DNA damage activates the HR- mediated DSB repair mechanism. This mechanism forms long single-stranded DNA to repair the doubleHolliday junction.

CPT is sometimes used as a second- or third-line treatment for endocrine-resistant breast cancer⁸.

3.7 Epigallocathechin Gallate 3(EGCG):

Mechanism action of EGCG:

EGCG initiates cell death through the intrinsic pathway and causes inhibition of EGFR, STAT3, and ERK pathways in several cancers. EGCG alters and inhibits ERK1/2, NF-κB, and Akt-mediated signalling, altering the Bcl-2 family proteins ratio and activating caspases in tumor cell⁹.

3.8 Baicalein:

Mechanism action of Baicalein: Baicalein was to determine whether it has the potential for therapeutic effects, such as arresting cancer cell growth via the MAPK pathway and apoptosis through ROS, 12lipoxygenase, and PI3K/Akt. and Wnt/β-catenin signalling pathways, as well as the EGFR/ERK, JNK signalling pathways and so on, which affect the expression of cell apoptosis-associated proteins. Baicalein affects the expression of cyclin and cyclin-dependent protein kinases (CDKs) to induce cell cycle arrest, oxidative radical scavenging, mitogen-activated protein kinase (MAPK), protein kinase B (Akt), mammalian target of rapamycin (mTOR), MMP-2/-9 (matrix metalloproteinase-2/-9) expression¹⁰ and caspase-9/-3 activation. This induces apoptosis and inhibits tumor invasion, metastasis, and progression.

3.9 Vincristine: Mechanism action of Vincristine:

Inhibition of microtubule polymerization: Vincristine interferes with microtubule polymerization by binding to tubulin subunits within the microtubule lattice. This binding prevents the addition of new tubulin subunits to the growing microtubule, thereby inhibiting microtubule elongation¹¹.

4. Active and passive targeting strategies for cancer therapy:

4.1 Active targeting strategy:

Chemotherapeutic agent-loaded nanocarriers can be conjugated with various targeting moieties, such as folic acid, monoclonal antibodies, or integrins, to enhance their specificity. These ligands can target:

a) Endothelial Cell Receptors: For example, integrin-αvβ3 and negatively charged phospholipids are preferentially expressed on tumor blood vessel endothelial cells

b) Tumor Cell Receptors: Receptors such as HER2 and folate receptors are often overexpressed on tumor cells

c) Lineage-Specific Targets: Some targets, like CD19, are expressed at similar levels on both tumor and normal Active targeting involves directing nanocarriers to tumor sites using targeting ligands that bind to receptors overexpressed on tumor cells or their vasculature, which are not present on normal cells, enabling selective targeting of tumor cells¹².

These targeting ligands facilitate the internalization of the nanocarriers into tumor cells via receptormediated endocytosis. However, several challenges must be addressed for effective deployment of active targeting strategies:

I. Extravasation and Binding: Liposomes may bind to the first line of targeted tumor cells in the interstitial compartment, hindering the accumulation of additional liposomes .

II. Endosomal Degradation: Nanocarriers may be internalized via endocytosis but often end up degraded in endosomes or lysosomes, limiting their therapeutic efficacy.

III. Rapid Clearance: Immunoliposomes designed for active targeting can be cleared from circulation more quickly than anticipated¹³.

Additionally, optimizing drug loading methods is crucial to prevent drug aggregation and ensure stability, enhancing the overall effectiveness of cancer treatments.

Passive Targeting: Enhanced Permeability and Retention (EPR) Effect:

In passive targeting, nanocarriers are directed into tumor tissue through leaky vasculature, relying on molecular movement via convection or passive diffusion. Tumor vasculature is characterized by chaotic and complex structures, extensive angiogenesis, and impaired lymphatic drainage. This results in high vascular permeability due to factors like bradykinin and nitric oxide, making the tumor vessels porous, with pore sizes ranging from 100 to 780nm, significantly larger than normal tissue junctions (less than 6nm)¹⁴. Due to this porous nature, nanocarriers in the bloodstream can selectively accumulate in tumor interstitial spaces.

Numerous nanocarriers have been explored for cancer treatment, utilizing both active and passive targeting strategies.

To optimize the therapeutic efficacy, controlled drug release at tumor sites is essential to minimize rapid metabolism and clearance. Drug release can be triggered by various stimuli, including exogenous factors (temperature, ultrasound, light, electric fields) and endogenous factors (pH changes, enzymatic activity, redox potential).

5. Herbal Nanostructures for Cancer Treatments:

A large number of nanocarriers with herbal compounds have been investigated for treatment of various types of cancer. These nanocarriers are a potential option for codelivery of drugs in treatment of cancer due to various attributes of drug targeting at the desired site, biodegradability, increased dosing interval, reduction in adverse effects, reduction in dose, nanosize improved stability and inability to deliver hydrophilic as well as hydrophobic drugs target cancer cells either by active targeting or passive targeting strategy.

5.1. Liposomes and Other Lipid Carriers:

5.1.1 Liposomes:

Liposomes are spherical vesicles made up of phospholipids which have a hydrophilic head and a hydrophobic tail. These phospholipids self-assemble under given conditions to form a bilayered structure called liposome. These liposomes have the ability to carry both hydrophobic and hydrophilic payload together. They have the advantages of high biocompatibility, biodegradability, ease of preparation, chemical versatility, and the ability to modulate the pharmacokinetic properties by changing the chemical composition and the components of the bilayers¹⁵.

5.1.2 Solid Lipid Nanoparticles (SLNs):

SLNs have gained significant attention in recent decades due to their favorable release profiles and targeted drug delivery capabilities, alongside excellent physical stability. Numerous studies have focused on enhancing the delivery of phytochemicals with anticancer properties using SLNs.

5.1.3 Micelles:

Polymeric micelles have garnered interest for their ability to deliver therapeutic agents specifically to targeted sites, reducing off-target toxicity and improving pharmacokinetics. Research has shown promising results with micelles loaded with agents like tea epigallocatechin gallate and Herceptin for cancer therapy. in 2014 reported that these nanomicelles demonstrated improved tumor selectivity, growth reduction, and longer blood half-lives compared to free Herceptin.

5.1.4 Dendrimers:

Dendrimers are hyperbranched polymeric structures that have gained significant attention for their versatility in drug delivery and high functionality. These nanostructured macromolecules can entrap or conjugate both hydrophilic and hydrophobic compounds through host–guest interactions and covalent bonding, respectively. Their high surface-to-volume ratio makes them particularly effective for gene delivery.

5.1.5 Inorganic Nanoparticles:

Inorganic nanoparticles, such as gold, iron oxides, zinc, and silicon, have been extensively investigated for their ability to deliver various anticancer phytochemicals in both preclinical and clinical settings. Additionally, Janus magnetic mesoporous silica nanoparticles (Fe₃O₄-mSiO₂) were developed for the magnetic targeting and delivery of berberine to hepatocellular carcinoma.

5.1.6 Nanocapsules:

Nanocapsules consist of a liquid or solid core containing a drug, encased within a polymer membrane made from natural or synthetic materials. They have gained considerable attention for their ability to provide sustained and controlled release of active ingredients.

5.1.7 Nanoemulsions:

Nanoemulsions are colloidal nanoparticles recognized for their stability and high loading efficiency. Characterized by solid spheres with an amorphous, lipophilic surface and a negative charge, they have gained traction in cancer therapy¹⁶.

Table No.1. Isolated compounds from different medicinal plants and their anticancer activities by the use of nanoparticles used to deliver different phytochemicals and the statuses of these studies were summerized.

Sr. No.	Main source of herbal compounds	Isolated compounds	Nanocarriers	Biological activity in cancer therapy	Status
1.	Rhizomes of curcuma longa	Curcumin	liposomes	Lung cancer treatment by means of downregulation of NF-kB in human lung cancer cell lines A549	In vitro and in vivo.
			Polymeric nanoparticles		In vitro.
			Silica nanoparticles		In vitro.
			Zno nanoparticles		In vitro.
			Nanoemulsion		In vitro.
			Nanohydrogel		In vitro.
			Magnetic nanoparticles		In vitro.
			Nanospheres		In vitro.
			Protein nanoparticles		In vivo.
			Lipid carriers		In vitro¹⁷.
2.	Berberis vulgaris¹⁸	Berberine	Solid lipid nanoparticles	Breast, liver and colon cancer (MCF-7, HepG2 and CACO 2)	In vitro.
			liposomes		In vitro and in vivo.
			Hybrid nanoparticles		In vitro and in vivo.
			Dendrimer		Ex vivo. and in
			Magnetic mesoporous silica nanoparticles		In vitro.
3.	Taxus brevifolia	Paclitaxel	Magnetic liposomes	Breast cancer and Ovarian	In vitro and in vivo.
			Solid lipid nanoparticles		In vivo.
			Dendrimer		In vitro.
			Polymeric micelles		Phase II, clinical trial
			Nanohydrogel		In vivo.
			Nanoemulsion		In vitro and in vivo.
			Nanocapsules		In vitro and in vivo.¹⁹
4.	Bark of japonica spohora	Quercetin	Nanoemulsion	Colon cancer cell lines HCT50 RKO breast cancer cells lines MCF-7, MDA-MB231, HBL1 00 and BT549 and Ovarian cancer cell lines, OVCAR5, TO V112D, OVCA R- 3and CAOV3	In vitro.
			Polymeric Nanocapsules		In vitro and in vivo.
			liposomes		In vitro.
			Micelles		In vitro and in vivo.
5.	Combretum caffrum	Combrestatin A-4	Mesoporous silica nanoparticles	Human Breast cancer and Ovarian cancer	In vitro and in vivo.
			Nanocells		In vitro and in vivo.
			liposomes		In vitro and in vivo.
			Nanocapsules		In vitro.
6.	Camptothecia acuminata	Campothecin	Polymeric nanoparticles	Second or third line treatment for endocrine resistant breast cancer	In vitro and in vivo.
			Magnetic cyclodextrin nanovehicles		In vitro.
			Dendrimer		In vivo.
			Mesoporous silica nanoparticles		In vivo.
			Nanoemulsion		In vitro and in vivo.
7.	Camellia sinensis	Epigallocat hechin gallate	Polymeric nanoparticles	Prostate cancer by induction of p53 dependent apoptosis. Also for ovarian cancer, liver and colon, cervical and breast cancerand lungs cancer.	In vitro and in vivo.
		Green tea	Polymeric nanoparticles		In vitro and in vivo.
			Polyphenols EGCG		In vivo.
		Epigallocat hechin 3 gallate	Liposomes		In vivo.
8.	Opium poppy	Noscapine	Magnetic Polymeric nanoparticles	Human prostate cancer progression and osteosacroma, colon cancer	Synthesis and charecterization
			Human serum albumin nanoparticles		In vitro.
			Polymeric nanoparticles		In vitro.
9.	Herb Scutellarin baicalensis	Baicalein	Solid lipid nanoparticles	In HEP-G2(hepatocellular carcinoma cell cluster) and MCF-7 (breast cancer cell cluster) cancer cells and SCC4 human tounge cancer cell.	In vivo.
			Self-assembled polymer nanoparticles		In vitro and in vivo.
			Liposomes		In vitro and in vivo.
			Magnetic nanoparticles		In vitro²⁰.
10.	Periwinkle plant Catharanthus roseus	Vincristine	Liposomes	Lymphocytic leukemia

6. Challenges and Future Prospect:

Although numerous nanomedicines have been investigated for the treatment of various cancers, only a limited number have successfully reached the market. A nanocarrier formulation must undergo a rigorous series of evaluations before commercialization. While most nanocarriers are developed based on the enhanced permeability and retention (EPR) effect, this effect is not uniformly present across all tumors and is rarely the sole determinant of nanocarrier efficacy²¹.

Improving the success rate of nanomedicines requires strategic decision-making frameworks, such as AstraZeneca’s 5Rs principle: right target efficacy, right tissue exposure, right safety, right patient, and right commercial potential. To develop cost-effective and superior therapies, the following key considerations must be addressed:

a) A clear understanding of clinical cancer heterogeneity and the biological factors influencing nanomedicine behavior in tumors.

b) A shift from formulation-driven research to disease-driven development.

c) Adoption of more relevant animal models and testing protocols.

d) Preselection of patients most likely to respond to nanomedicine therapies.

Nanocarriers provide promising and innovative strategies for cancer treatment, however nanocarriers provide effective treatment with minimize side effect.

7. CONCLUSION:

The global cancer mortality rate continues to rise. In response to this growing health burden, a wide range of herbs and their extracts have been traditionally utilized for cancer treatment. Today, bioactive compounds derived from these herbs are being explored for their effectiveness against different types of cancer. Given the severe side effects associated with conventional therapies, researchers have increasingly investigated the use of nanocarriers to deliver herbal compounds or their derivatives. These herbal compound-loaded nanocarriers have demonstrated the ability to efficiently deliver drugs to tumor sites, reduce therapy-related side effects, and enhance tumor cell eradication. They can target cancer cells either through passive targeting mechanisms such as the enhanced permeability and retention (EPR) effect or through active targeting strategies involving specific ligand-receptor interactions. Although numerous nanocarriers have been developed and evaluated for cancer therapy, only a few have reached the market due to stringent preclinical assessments and complex regulatory approval processes. The success rate of these nanomedicines can be improved by adopting efficient decision-making strategies, such as AstraZeneca’s 5Rs framework: the right target, right tissue, right safety, right patient, and right commercial potential.

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Received on 24.06.2025 Revised on 02.08.2025

Accepted on 01.09.2025 Published on 02.01.2026

Available online from January 05, 2026

Asian J. Res. Pharm. Sci. 2026; 16(1):79-84.

DOI: 10.52711/2231-5659.2026.00013

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

1. INTRODUCTION:

2. IMPORTANCE OF NANOMEDICINES:

3. Herbal compounds for cancer therapy:

5. Herbal Nanostructures for Cancer Treatments:

7. CONCLUSION:

8. REFERENCES: