Table 5 Potential pre-clinical lysosome-targeted interventions for tumors

Autophagy activator

Rapamycin

Rapamycin suppresses M2 macrophage polarization

[253]

Sorafenib

Sorafenib suppresses classical macrophage activation

[324]

Autophagy inhibitor

Hydroxychloroquine

Chloroquine and hydroxychloroquine switches TAMs from M2 to M1 phenotype

[275, 276]

Chloroquine

Bafilomycin A1

Bafilomycin A1-induced M1-like polarization by preventing NF-κB degradation

[256]

3-Methyladenine

3-Methyladenine prevents cross-talk between cancer cells and CAF through autophagy

[305]

Cathepsin B inhibitor

CA074Me

CA074Me inhibits cell invasion and inflammasome activation

[192, 289]

CA-074

CA-074 inhibits EMT

[195]

Cathepsin S inhibitor

Fsn0503

Fsn0503 inhibits cell invasion

[286]

Cathepsin L inhibitor

Z-FY-CHO

Z-FY-CHO inhibits radio-resistance

[214]

KGP94

KGP94 and KGP207 inhibits cancer cell invasion and M2-like TAMs

[284]

KGP207

General cysteine cathepsin inhibitor

E64

E64 inhibits cell invasion

[283]

JPM-OEt

JPM-OEt inhibits drug resistance, tumorigenesis, angiogenesis, proliferation, and invasion

[197, 254, 279]

Transfection vehicle

Ghost

Ghost is applied for transfection of LAMP2A siRNA in TAMs

[260]

PEG = MT/PC NPs

PEG = MT/PC NPs is applied for transfection of VEGF and PIGF siRNA

[330]

Porous silicon micro-particles

Porous silicon micro-particles is applied for delivering HER2 antigen into DCs

[334]

Lipid-coated calcium phosphate nanoparticles

Lipid-coated calcium phosphate nanoparticles is applied for delivering antigen TRP2 mRNA and PD-1 siRNA

[335]

Metal–organic framework

Metal–organic framework is applied for delivering tumor-associated antigens into macrophages

[336]

TAM remover

M-chlorin

M-chlorin can enter lysosomes and delete M2 macrophages

[430]

DOX-SPCL

DOX-SPCL concentrates in lysosomes and delete macrophages

[332]

MEN 4901/T-0128

MEN 4901/T-0128 releases cytotoxic T-2513 in lysosomes

[333]

TLR3 agonist

Poly(I:C)

Poly(I:C) activates M1 macrophages

[262]

TLR4 agonist

LPS

LPS activates M1 macrophages

[262]

Polyethyleneimine

Polyethyleneimine reverses M2-like polarization

[264]

Cationic dextran

Cationic dextran reverses M2-like polarization

[264]

Multiwalled carbon nanotubes

Multiwalled carbon nanotubes reverses M2-like polarization

[265]

TLR7 agonist

CL264

CL264 reverses M2-like polarization

[262]

1V270

1V270 reverses M2-like polarization

[266]

Gardiquimod

Gardiquimod increases M1-like polarization

[267]

Let-7b

Let-7b reverses M2-like polarization and suppresses IL-10 production

[268]

R848

R848 increases M1-like polarization

[269]

R837

R837 enhances anti-tumor immunity

[338]

TLR9 agonist

CpG ODN

CpG ODN potentiates antigen presentation in macrophages

[270]

Other

Spermine modified pullulan

Spermine modified pullulan can enter lysosomes and reprogram M2 macrophages to M1

[337]