1 Introduction

Breast cancer is a significant health issue worldwide, with 2.3 million women being diagnosed with breast cancer and 670,000 deaths reported globally in 2022 alone. According to global statistics, in countries with a very high Human Development Index (HDI), 1 out of 12 women will be diagnosed with breast cancer during their lifetime, and 1 out of 71 women may die from this disease [1, 2]. The global market for breast cancer therapeutics has witnessed substantial metamorphosis in recent years, driven by advancements in research, premature detection approaches, and pioneering treatment options. Additionally, the emergence of nanotechnology has furnished new avenues for designing novel formulations with enhanced bioavailability and reduced side effects. Even with advances in conventional therapy, including surgery, chemotherapy, and radiation therapy, there are existing limitations in effectively targeting and controlling breast cancer [1, 3]. Epigallocatechin gallate (EGCG), a green tea polyphenol, has demonstrated as a potential candidate for breast cancer suppression and treatment [4]. The EGCG implicates a substantial induction in the angiogenesis of cancer cells, proliferation, and metastasis, thereby providing an oxidative environment, re-modeling and re-programming immune cells, and extracellular matrix, rejuvenating chemoresistance [5], furthermore summarized in graphical abstract. EGCG can modulate several signaling pathways crucial to breast cancer progression. Breast cancer is a serious concern, and scientists have been working hard to understand the different pathways involved in it. Among these pathways, the PI3K/Akt/mTOR pathway has been extensively studied and found to be frequently dysregulated in breast cancer [6], further summarized in Fig. 1a. The abnormal signaling of the PI3K-Akt pathway, a key mediator of increased mitogenic signaling, has been established as a crucial step in the initiation and progression of human tumors, as supported by epidemiological and experimental studies. Consequently, targeting the PI3K-Akt pathway has been recognized as a promising therapeutic strategy for treating various types of cancer. It is indeed true that blocking this pathway inhibits both the proliferation and growth of tumor cells and sensitizes them to programmed cell death, enhancing its appeal as a cancer therapeutic target [7].

The conventional delivery of EGCG faces several challenges that limit its therapeutic efficacy and clinical translation. EGCG is highly susceptible to degradation due to exposure to light, oxygen, and pH changes [8]. EGCG exhibits low oral bioavailability due to pharmacokinetic challenges, i.e., limited absorption, extensive metabolism, and first-pass metabolism in the liver. As a result, only a small fraction of orally administered EGCG reaches systemic circulation, reducing its therapeutic effectiveness. Systemic administration of EGCG can lead to off-target effects and systemic toxicity, as EGCG interacts with various biological molecules and pathways throughout the body. EGCG has a relatively short half-life in vivo, leading to the rapid clearance of EGCG from the bloodstream and limiting its duration of action. EGCG's hydrophobic nature, poor penetration through biological barriers, and propensity for degradation pose challenges for formulating stable and bioavailable dosage forms [8, 9]. Developing suitable formulations for EGCG delivery that preserve its stability, enhance its solubility, and improve its bioavailability is a significant hurdle in conventional delivery approaches. Addressing these challenges requires innovative strategies that enhance EGCG's stability, improve bioavailability, and enable targeted delivery to diseased tissues while minimizing off-target effects [10]. Nanoparticle-based delivery systems, such as lipid-based formulations, are among the strategies explored to overcome these limitations and enhance the therapeutic potential of EGCG in various disease settings [11, 12].

Therefore, this brief communication strives to comprehend and highlight the prophylactic phytocompound EGCG exhibited potential anti-cancer properties, including anti-inflammatory, anti-proliferative, and anti-angiogenic effects. Furthermore, we have also reworded the limitations associated with EGCG and, thus, loaded into a lipid-based drug delivery system for further improvement of therapeutic potential and stability of the phytocompounds. The brief communication also writes to modulate several signaling pathways crucial to breast cancer progression.

2 Potential targeting of breast cancer via EGCG loaded delivery approaches

EGCG can impede this pathway, diminishing cell survival and proliferation and augmenting sensitivity to chemotherapy. Additional pathways targeted by EGCG include the MAPK, nuclear factor-κB (NF-κB), and Wnt/β-catenin pathways, all of which have implications for breast cancer development and progression [4, 5]. According to a study, anti-proliferative effects of EGCG loaded into PEGylated Folic acid nanoconjugates were observed in a concentration-dependent manner, effectively inhibiting the proliferation of the MCF-7 cell line. These nanoconjugates achieved this by influencing the expressions of several crucial regulatory proteins within the PI3K-Akt pathway. Specifically, EGCG promotes or upregulates the expression of PTEN, p21, and Bax while downregulating the expression of p-PDK1, p-AKT, CyclinD1, and Bcl-2. Importantly, these effects were achieved with minimal side effects and the most negligible cytotoxicity when tested by methylene blue assay [13]. EGCG exhibits anti-angiogenic impacts by impeding the production of pro-angiogenic factors, i.e., vascular endothelial growth factor (VEGF), thereby controlling angiogenesis and limiting the nutrient supply to the tumor [14]. While EGCG exhibits guarantee as a potential therapy for breast cancer, it is paramount to consider its limitations. EGCG has poor bioavailability, undergoes rapid metabolism, and has limited systemic distribution, resulting in lower concentrations at the tumor site. Being susceptible to oxidation, degradation, and enzymatic inactivation, EGCG's stability can be affected by temperature, pH, and light exposure. The stability of EGCG must be retained during formulation, storage, and administration, which is necessary for its therapeutic efficacy [15, 16].

To address these limitations, a distinctive investigation suggested the rationale of nano chemoprevention, which involves leveraging nanotechnology to enhance the pharmacokinetics and pharmacodynamics of chemopreventive targets for cancer management [17]. Additionally, EGCG has shown potential as an adjuvant in chemotherapy. It has exemplified synergistic effects with typically used anti-cancer drugs such as doxorubicin, tamoxifen, and paclitaxel across various cancer cell lines [18]. Several studies documented in the scientific literature have employed nanotechnology approaches, utilizing diverse types of nanoparticles as delivery vehicles for EGCG, intending to target different cancer types in laboratory settings (in vitro) and animal models (in vivo) [19]. The encapsulation of EGCG within lipid-based nanoparticles has acquired substantial attention as a delivery system for enhancing the therapeutic potential of EGCG in various applications, including breast cancer treatment [20]. Their biocompatibility, biodegradability, high drug-loading capacity, specific targetability, and improved solubility and stability drive them inviting for various biomedical applications. Lipid-based nanoparticles can be classified according to the types of lipids used in their formulation or based on their structural organization, which may include liposomes, micelles, lipid-coated nanoparticles, and lipid-drug conjugates [21]. Liposomes are spherical vesicles composed of lipid bilayers, while micelles are colloidal structures formed by self-assembly of lipid molecules in aqueous solutions. Lipid-coated nanoparticles feature a solid or liquid core surrounded by a lipid monolayer, providing stability and enhanced drug loading capacity. Lipid-drug conjugates involve covalent attachment of therapeutic agents to lipid molecules, improving solubility and targeting capabilities [22, 23]. This classification facilitates the rational design and optimization of LNPs for specific biomedical applications, lead to the development of advanced nanomedicines with enhanced efficacy and safety profiles [24]. Lipid nanocarriers can be sub-categorized into two broad sections, namely, Solid lipid nanoparticles (SLNs), and Nanostructured lipid carriers (NLCs) [25, 26]. SLNs are colloidal lipid-based nanoscale particles composed of solid lipids. Solid lipids provide improved stability to the encapsulated drug, protecting it from degradation and maintaining its bioactivity. SLNs have an excellent possibility for delivering hydrophobic and hydrophilic drugs, including small molecules, peptides, and nucleic acids. NLCs are another type of lipid nanocarrier that has gained considerable attention [27]. NLCs consist of a blend of solid and liquid type of lipids, resulting in a more structurally stable system compared to SLNs. The incorporation of liquid lipids into the lipid matrix reduces the crystallinity and improves the drug-loading capacity of NLCs. This distinctive structure allows for the encapsulation of a wide range of drugs with different physicochemical properties. NLCs offer advantages such as enhanced drug solubility, drug stability, and prolonged release profiles [28]. According to a recent research, Paclitaxel-loaded liposome into chitosan/polycaprolactone nanosystem elicited higher cytotoxicity against MCF-7 cell line (i.e., breast cancer cell line) with an efficiency of 85 ± 2.5%. Significant reduction of tumor weight was observed from 1.35 ± 0.15 gm to 0.65 ± 0.05 gm within 30 days by achieving sustained release of the chemotherapeutic from the liposomal incorporated polymeric nanosystem [29]. The downregulated expression of hypoxia-inducible factor 1 (HIF-1) and other signaling pathways via EGCG have been further summarized in Fig. 1b.

Fig. 1
figure 1

a Understanding of molecular mechanisms of (−)-EGCG downregulation through various signaling pathways such as the NF-κB, PI3K/AKT, and Wnt, to inhibit cellular proliferation and inflammation and induce apoptosis. b Graphical representation understanding the molecular mechanisms of EGCG downregulated expression of HIF-1 and other signaling pathways (PI3K/AKT, NF-κB, and MAPK) to inhibit metastasis and angiogenesis [34]

Full size image

Despite the challenges posed by the reactivity and instability of tea catechins, various strategies have been proposed to mitigate these issues and enhance their therapeutic efficacy. EGCG, despite its well-documented health benefits, faces significant limitations related to its poor bioavailability and stability [30, 31]. Upon oral administration, EGCG encounters barriers such as low intestinal absorbance and rapid degradation in the gastrointestinal tract, resulting in limited systemic exposure and reduced therapeutic efficacy [32]. Moreover, within the acidic microenvironment of cancer cells, EGCG's instability further compromises its effectiveness, hindering its ability to exert anti-cancer effects. Nanocarriers, including lipid-based nanoparticles, provide a protective environment for EGCG, shielding it from degradation and improving its stability during transit through the gastrointestinal tract. Additionally, nanocarriers can facilitate targeted delivery of EGCG to cancer cells, demonstrating the enhanced permeability and retention (EPR) effect and active targeting ligands to achieve selective accumulation within tumor tissues [9, 33].

3 Conclusion

The EGCG is a polyphenol found in green tea and has gained significant attention for its potential health benefits, including its role as a chemoprotective agent. EGCG can neutralize free radicals, reduce inflammation-induced damage to cells and tissues, trigger apoptosis through various pathways, including activation of pro-apoptotic proteins and inhibition of anti-apoptotic proteins, inhibition of angiogenesis and metastasis, modulation of signaling pathways, etc., identify EGCG as a potential agent for anti-cancer therapy or chemoprotective agent. The future for EGCG-loaded lipid nanocarriers lies in their translation from bench to bedside. Further research is required to optimize the lipid nanocarrier formulation, including lipid composition, size, and surface modifications, to maximize EGCG encapsulation efficiency, stability, and targeting capabilities. Furthermore, comprehensive pharmacokinetic and toxicity studies and large-scale manufacturing procedures are indispensable for their clinical development. The current market size of breast cancer therapeutics reflects the rising demand for ground-breaking treatment options. Nano-based formulations offer extraordinary prospects for overcoming the limitations of conventional therapies and improving patient outcomes. Continued research and development in this field are necessary to clinically translate these promising findings into viable solutions that can benefit breast cancer patients worldwide.