## 7 Nanoplatforms, Natural Products, and Resistance
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Natural Compound** & **Nanoformulation** & **Drug** & **Main Results on MDR Effect** & **Reference** \\ \hline Curcumin & Alginate nanodroplet & DOX and curcumin & Increased in vitro cytotoxicity and 5-fold tumor & \\  & Chitosan/poly (butyl & & inhibition in in vivo DOX-resistant A2780 ovarian tumor model. & [92] \\ Curcumin & cyanoacrylate) (FBCA) NP & DOX and curcumin & Decreased Pgp expression in DOX-resistant MCF-7 & \\  & & & human breast carcinoma cell line. & [93] \\ Curcumin & NVA622 NP & DOX and curcumin & Increased nuclear accumulation of DOX in & \\  & & & DOX-resistant ovarian, prostate, and multiple & \\  & & & myeloma tumor cell lines. & [94] \\ Curcumin & Poly (lactic-co-glycolic acid) (PLGA) NP & DOX and curcumin & 12-fold decrease in MDR1 and BCL-2 mRNA & \\  & & & expression and increased nuclear retention of DOX & \\  & & & in chronic myeloid leukemia (CML) blasts like & \\  & & & K562 cells. & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Nanoformulations loaded with natural products to overcome MDR. Quercetin is another of the most studied natural compounds for nanomaterial-based delivery, which has been used to reduce MDR and cardiotoxicity associated with anthracy  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Natural Compound** & **Nanoformulation** & **Drug** & **Main Results on MDR Effect** & **Reference** \\ \hline \multirow{4}{*}{ \begin{tabular}{c} Curcumin \\ \end{tabular}  } & PEG2000-DSPE/d-a- & & & Increased cellular entry in time-dependent manner, \\  & tocepheryl poly-ethylene & & & enhanced intracellular accumulation, and reduced \\  & glycol succinate 2000 & & & DOX efflux in DOX-resistant MCF-7 human breast \\  & (TPCS200) mixed micelle & & & carcinoma cell line. \\  & & & & Decreased more than 80\% Pgp protein expression \\  & & lipid nanoparticle & & & in DOX-resistant MCF-7 human breast carcinoma \\  & & & & cell line. \\  & & & & cell line. \\  & & & & Decreased Pgp and NF=8 expression in \\  & & & & paclitaxel-resistant SK-OV-3 TBR human ovarian \\  & & & adenocarcinoma cells. \\  & & & & Decreased gene and protein expression of MRP-1 \\  & & & & and LRP by curcumin in dose-dependent manner \\  & (PLGA) NP & & & in Y79 human retinoblastoma cells. \\  & & & & \\  & Poly (ethylene & & & \\  & & & &  
cline therapy [114]. In this regard, the study by [PERSON] et al. on mixtures of polymeric micelles transporting DOX and quercetin showed downregulation of Pgp expression, increased intracellular drug concentration, and, therefore, improved cytotoxicity compared with free DOX in the breast tumor cell line MDA-MB-231/MDR1 [109]. The same result was found in an in vitro and in vivo study of biotin-conjugated polymeric nanoparticles in a DOX-resistant MCF-7 breast tumor model [110]. Catechin is another flavonoid compound found in green tea that has been studied for its MDR-modulating role, specifically as an effective modulator of Pgp. [PERSON] et al. formulated polyion complex micelles loaded with DOX and EGCG that were shown to enhance cell entry and increase toxicity compared with a formulation without ECGC and free DOX in DOX-resistant MCF-7 cells [111]. A study of the triterpeno sachymic acid and dehydrotumulosic acid purified from an extract of Poria cocos is particularly noteworthy. Their encapsulation in a liposome together with DOX was shown to reduce the protein expression of Pgp and caveolin-1 and resulted in an enhanced antitumor effect in vivo in a DOX-resistant MCF-7 breast tumor model compared with other single-therapy groups [112]. Nanofomulations based on natural products comprise a new field of research in which natural products are used to synthesize nanocarriers with improved results in toxicity, bioavailability, and pharmacological activity, among others [90]. In this context, [PERSON] et al.