Table 2 Polymeric and liposomal nanomaterials used to reverse cancer MDR

1

Tween 80 and PEG coated PBCA NPs

Doxorubicin

Human colon (SW620 and SW620/Ad300) and NSCLC (NCI-H460 and NCI-H460/MX20)

PEG and Tween 80 act as P-gp inhibitors and block the doxorubicin efflux from the cells and doxorubicin mediated toxicity

[261]

2

PLGA NPs

Doxorubicin and Verapamil

Human breast cancer (MCF-7 cells)

Inhibition of P-gp efflux pump and enhanced accumulation of drugs and cytotoxicity

[262]

3

Nano PEG-ADDC

Irinotecan and YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole)

Non small cell lung cancer (A549 cells)

Downregulation of HIF-1α and VEGF proteins also enhanced intracellular drug retention

[263]

4

Folate-biotin conjugated starch NPs

siRNA-IGF1R and Doxorubicin

Human lung carcinoma (A549 cells)

Downregulation of IGF1R protein expression and drug uptake and cytotoxicity

[264]

5

HPMA-gelatin NPs

Doxorubicin and Glycyrrhetinic acid (GA)

Human hepatoma (HepG2 and HepG2/ADR cells) and BLAB/c nude mice

P-gp efflux pump downregulation by GA, enhanced mitochondrial ROS generation, higher uptake of drugs in cells and suppression of tumor growth

[265]

6

Folate modified DSPE-MPEG-PLGA NPs

Phephobide a (Pba)

Human gastric (MKN 28 cells) and nude mice

Bypass the P-gp efflux pump and elevated levels of intracellular drug accumulation

[266]

7

Hyaluronic acid conjugated PLGA NPs

Paclitaxel and FAK specific siRNA

Human ovarian cancer (A2780, A2780-CP20 cells, SKOV3, SKOV3-TR, HeyA8 and HeyA8-MDR cells) and PDX mouse model

FAK gene silencing, enhanced accumulation of drug, bypassing the P-gp efflux pumps and suppression of tumor growth and development in PDX models

[81]

8

PEG-PLA NPs

Cyclosporin A and Gefitinib

Human non-small cell lung cancer (PC-9 and PC-9-GR cells, H1975 cells) and BALB/c mice PC-9-GR and H1975 xenografts

Inhibit EGFR tyrosine kinase disturb the downstream STAT3/Bcl-2 signaling transduction of leads to inhibition of cancer cell progression

[153]

9

TPGS-PLGA NPs

Doxorubicin and Metformin

Human breast cancer (MCF-7/DOX cells)

Inhibit P-gp to reduce drug efflux and enhance intracellular doxorubicin accumulation and reduce the cellular ATP content

[147]

10

Mannosylated albumin NPs

Disulfiram/Cu complex and regorafenib

Human cells (HCT8/ADR and HUVEC cells) mouse macrophage cells (RAW 264.7 and L929 cells)

Chemosesitization through ROS generation and enhanced apoptotic cell death

[267]

11

FA-PEI-PEG conjugated nanographene

P-gp specific siRNA (siP-gp) and Doxorubicin

Human breast cancer (MCF-7 and MCF-7/ADR cells)

siRNA-mediated P-gp gene silencing, enhanced doxorubicin retention and toxicity

[268]

12

Amphiphilic poly-Jug-DA-b-PEG NPs

P-gp specific siRNA (siP-gp) and Doxorubicin, Juglanin

Human lung cancer (A549 and H69 cell lines) and nude BLAB/c mice

Inhibition of P-gp gene silencing, drug uptake, inhibiting tumor growth

[269]

13

Anisamide-PLGA NPs

Resveratrol and Doxorubicin

Human breast cancer cell lines (MCF-7/ADR, MDA-MB-231/ADR cells) and BALB/c nude mice

Inhibition of the expression of MDR-linked transporters P-gp, MRP-1, BCRP and downregulation of NF-κB to enhance apoptosis

[270]

14

Chitosan modified TPGS-b-(PCL-ran-PGA) NPs

siHIF and Cisplatin

Human nasopharyngeal cancer cell line (CNE-2 cells)

MDR1/P-gp gene silencing via siHIF gene and enhanced sensitivity of cisplatin to cells

[175]

15

PLGA-TPGS NPs

Docetaxel and Poloxamer 235

Human breast cancer (MCF-7/TXT cells) and SCID mice

P-gp inhibition and docetaxel accumulation and tumor suppression

[271]

16

Chitosan NPs

Gefitinib and shMDR1 gene

Gefitinib resistant HeLa cells

shMDR1-mediated anti-DNA enzyme degradation activity and inhibition of MDR1 gene expression

[272]

17

TPGS conjugated chitosan NPs

Doxorubicin

Human hepatocarcinoma (HepG2 and BEL-7402) and human breast cancer (MCF-7/DOX cells) and BEL-7402/5-Fu cells

NP-mediated P-gp efflux pump blocking and downregulation of cellular ATP levels

[273]

18

mPEG-b-PLA polymersomes

Bcl-xL siRNA and Doxorubicin

Human gastric cancer (MKN-45 and MKN-28 cell lines)

siRNA-mediated downregulation of Bcl-xL, enhanced intracellular drug retention and reversal of MDR

[274]

19

Chitosan-PBCA NPs

Curcumin and Doxorubicin

Human breast cancer MCF-7 and MCF-7/ADR cells

Downregulation of P-gp efflux pump, NF-κB and elevated level of drug retention and cytotoxicity

[275]

20

Folate-PLGA NPs

Nutlin-3a and Curcumin

Human retinoblastoma Y79 cells

Curcumin-mediated MRP-1 and LRP downregulation via modulation of NF-κB translocation

[246]

21

PLGA NPs

Doxorubicin

Human ovarian (SKOV-3) and uterine (MES-SA/Dx5) cells

Drug resistance is overcome via enhancing intracellular drug uptake and nuclear retention

[276]

22

PLGA NPs

Curcumin and Doxorubicin

Human leukemia (K562) cells

Curcumin-mediated P-gp inhibition, downregulation of MDR1, NF-κB and Bcl-2 gene expression

[277]

23

AOT-Sodium alginate

Methylene blue and Doxorubicin

Primary mammary adenocarcinoma cells (JC cells) and female BALB/c mice

Methylene blue acts as P-gp inhibitor, enhances the inhibition of tumor progression and increases apoptotic mechanisms

[278]

24

Dextran sulphate-PLGA hybrid NPs

Vincristine sulfate

Human breast cancer (MCF-7 and MCF-7/ADR)

Inhibition of P-gp efflux ability by blocking of efflux transporter by NPs and enhanced intracellular drug retention

[279]

25

NIPMAm based core–shell hydrogels

siRNA and Docetaxel

Human ovarian cancer cell lines (Hey and SKOV-3 cells)

Loss of EGFR expression due to EGFR gene silencing via siRNA for increased sensitivity of docetaxel

[280]

26

Folic acid conjugated hydroxypropyl chitosan NPs

Antisense oligodeoxynucleotides as ODNs

Human carcinoma dox resistant cells (KB-A-1 cells) and BALB/c nu/nu KB-A-1 xenograft mice

Inhibition of expression of MDR1 gene and P-gp efflux pumps

[281]

27

Biotin conjugated PLGA-PEI NPs

Paclitaxel and P-gp targeting siRNA

Primary mammary adenocarcinoma cells (JC cells) and female BALB/c mice

Enhanced intracellular retention of paclitaxel and silencing of MDR1 gene that encodes for P-gp efflux pump

[282]

28

Biotin-PLGA NPs

Tariquidar and Paclitaxel

Ovarian cancer cell lines NCI/ADR-RES cells and BLAB/c mice

Inhibition of P-gp pump-mediated drug efflux from cells, enhanced drug retention and cytotoxicity and tumor growth inhibition

[283]

29

PLGA NPs

Vincristine and Verapamil

Human Breast cancer cells (MCF-7/ADR cells)

P-gp inhibition via verapamil and elevated intracellular drug retention

[284]

30

PEO-modified PBAE NPs

MDR1 gene silencing siRNA and Paclitaxel

Ovarian cancer (SKOV and SKOV3_TR) cells

Anti-MDR1 gene silencing via siRNA leads to drug retention and cytotoxicity in cells

[285]

31

PEO modified PLGA/PBEA blend NPs

Paclitaxel and Ceramide

Human breast cancer (MCF-7 and MCF-7_TR cells) and MCF-7/ADR nu/nu xenograft model

Enhanced intracellular accumulation and lower clearance rate of paclitaxel

[286]

32

PEO-PCL NPs

Paclitaxel and C6-ceramide

Ovarian cencer (SKOV3 and SKOV3_TR) and nu/nu xenograft model

Drug combination enhances apoptosis and inhibits tumor progression

[287]

Liposomal nanoformulations

33

TPGS-liposomes

Docetaxel and Coumarin-6

Human lung cancer (A549 and A549/DDP cells) and nude mice

Inhibition of P-gp pump activity preventing the efflux of drug from cells. Enhanced intracellular and antitumor activity of drugs

[107]

34

Protoporphyrin IX (PpIX) doped liposome

Doxorubicin

Human breast cancer (MCF-7/ADR cells) and nude mice

Photodynamic-mediated disruption of P-gp efflux pumps by PpIX with enhanced intranuclear drug accumulation and suppression of tumor growth

[108]

35

Amphiphilic cationic phospholipids

Cabzitaxel and silibinin

Prostate cancer (PC-3 and DU-145 cells)

Active targeting of CD44 cell markers to target CSCs and overcome MDR

[288]

36

PEG-PLL-DMA Liposome

NO donar (DETA NONOate) and Paclitaxel

Human lung cancer (A549/T cells) and nude mice

Enhanced drug release and accumulation and downregulation of the expression of P-gp efflux pump with suppression of tumor development

[289]

37

Liposome

Doxorubicin and Aptamer AS1411

Human breast cancer (MCF-7/ADR cells)

Enhanced nuclear uptake, release of drug in nuclei and bypassing P-gp efflux pumps

[290]

38

CL-R8_LP-SPC:CHO:CHO-PEG₂₀₀₀-R8:CHO-S–S-PEG₅₀₀₀

Doxorubicin and verapamil

Human breast cancer (MCF-7 and MCF-7/ADR cells)

Liposome-mediated P-gp bypassing for intracellular drug retention and enhanced cytotoxicity

[105]

39

Liposome (Lipodox)

Doxorubicin

Human colon cancer (HT29 and HT-29-dx cells)

Alteration of the P-gp raft composition with impaired P-gp transport function and ATPase activity

[76]

40

Liposome polycation DNA (LPD) NPs

siRNA (VGFR and c-myc) and Doxorubicin

Ovarian cancer cell lines (NCI/ADR-RES and OVCAR-8 cells) and NCI/ADR-RES xenograft female nude mice cells

siRNA-mediated silencing of MDR1 gene. Lipid NPs also act as P-gp inhibitors with elevated levels of intracellular Doxorubicin

[291]

41

Amphiphilic phospholipid and cholesterol with transferrin

Doxorubicin and verapamil

Leukaemia (K562 and K562/DOX) cells

Inhibition of the P-gp efflux pump

[292]

42

Anti-transferrin receptor monoclonal antibody (OX26 mAb) conjugated liposome

Digoxin and Propidium Iodide

Rat brain capillary endothelial cells (RBE4)

OX26 mAb and digoxin conjugated liposomes effectively bypass the P-gp efflux pump

[106]

43

Cardiolipin-phosphotidylcholine based liposomes

Doxorubicin

Human breast cancer (MCF-7, MCF-7/ADR) and ovarian cancer (SKOV3, SKVLB) cells

Liposomal formulation modulates the intracellular drug distribution and retention

[293]

44

Liposome

Doxorubicin

Human leukemia (HL-60/VCR, HL-60/ADR cells)

Inhibition of the P-gp drug efflux pump via direct interaction, with elevated intracellular drug retention

[294]

Solid Lipid Nanoparticles (SLNs)

45

SLNs

Linagliptin

Human colorectal cancer (Caco-2 cells) and Albino Wistar rats

Inhibition of P-gp drug efflux and lymphatic targeting

[222]

46

SLNs

Curcumin

Human breast cancer (MCF-7, MDA-MB-231) cells and murine mammary (JC cells) and BALB/c mice

Inhibition of Akt/IKKα-β/NF-κB signaling and inhibition in transcriptional activation of P-gp promoter p65/p50 NF-κB

[295]

47

SLNs

Doxorubicin and Quinazolinone derivative (QZO-DER)

Human colorectal cancer (HCT-116 cells), human lung carcinoma (A549 cells) and human breast cancer (MCF-7 and MDA-231 cells)

Enhanced cellular uptake of SLNs conjugated with drugs and associated cytotoxicity to cell lines

[296]

48

SLNs

Paclitaxel

Human breast cancer (MCF-7, MCF-7/ADR cells)

Intracellular uptake of drug and evasion of the P-gp efflux pumps

[297]

50

Nanolipid carriers (NLCs)

β-lapachone and Doxorubicin

Human breast cancer (MCF-7/ADR cells) and BLAB/c nude mice

Lapachone inhibits P-gp expression, diminishes ATP levels and downregulates HIF-1α and NF-κB expression

[298]

51

TPGS-Brij78 coated SLNs

Curcumin and Piperine

Human ovarian resistant cancer (A2780/Taxol cells)

TPGS and Brij78-mediated P-gp inhibition with enhanced drug retention and elevated cytotoxicity

[299]

52

SLNs

Paclitaxel and Curcumin

Human breast cancer (MCF-7/ADR) cells

Curcumin inhibits P-gp expression and enhances intracellular drug retention and cytotoxicity

[300]

53

Nanolipid carriers (NLCs)

Doxorubicin and Vincristine

B-lymphoma (LY-I cells) and BALB/c mice

Enhanced intracellular uptake, bypassing the P-gp efflux pump and improved suppression of tumors

[301]

54

Cholesterol-PEG coated SLNs

Doxorubicin

Human breast cancer (MCF-7, MCF-7/ADR cells) and xenograft nude mice

Inhibition of P-gp drug efflux activity, enhanced drug retention and cytotoxicity

[302]