A Conjugate for delivery of a drug across biological membranes, the Conjugate having the structure as set forth in Formula: or pharmaceutically acceptable salts, hydrates, solvates and metal chelates of the compound represented by the structure as set forth in Formula, and solvates and hydrates of the salts, wherein: D is the drug to be delivered across biological membranes, selected from a group consisting of a small-molecule drug, a peptide, a protein, and a native or modified, single-stranded or double-stranded DNA or RNA, siRNA or ASO; y, z and w are each an integer, independently selected from 0, 1, 2, 3, 4, 5 or 6, wherein whenever the integer is 0, it means that the respective E moiety is null; at least one of y, z or w is different from 0; E, E', or E" can be the same or different, each having the structure selected from: in the case that a=1, k=1; the moiety is designated Apo-Si-G wherein L 2 and L 3 are each selected from null and the group consisting of::linear, cyclic or branched C 1, C 2, C 3, C 4, C 5, C 6, C 7, C 8, C 9, C 10, C 11, C 12, C 13 or C 14, alkyl or hetero-alkyl, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, or thiol; or linked to an ether group; linear, cyclic or branched C 2, C 3, C 4, C 5, C 6, C 7, C 8, C 9, C 10, C 11, C 12, C 13 or C 14 alkylene or heteroalkylene, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, thiol; or linked to an ether group; C 5, C 6, C 7, C 8, C 9, C 10, C 11, C 12, C 13 or C 14 aryl or heteroaryl, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, thiol; or linked to an ether group; -(O-CH 2 -CH 2) u -, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, or thiol; nucleoside, nucleotide; imidazole, azide, acetylene; and any combinations thereof, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, thiol; or linked to an ether group; and wherein u is an integer of 1, 2, 3, 4 or 5; and any combinations thereof; and W and G are each independently selected from null, oxygen, ester, amide or secondary or tertiary amine groups; a, b, k and d each stands independently for integer of 0, 1, 2, 3, 4, 5 or 6; R', R", R′′′ and R IV are each selected from the group consisting of hydrogen, methyl and ethyl; and U is selected from the group consisting of null, -O-, ester, amide, and amine (secondary or tertiary amine). D is the drug to be delivered across biological membranes, selected from a group consisting of a small-molecule drug, a peptide, a protein, and a native or modified, single-stranded or double-stranded DNA or RNA, siRNA or ASO; y, z and w are each an integer, independently selected from 0, 1, 2, 3, 4, 5 or 6, wherein whenever the integer is 0, it means that the respective E moiety is null; at least one of y, z or w is different from 0; E, E', or E" can be the same or different, each having the structure selected from: in the case that a=1, k=1; the moiety is designated Apo-Si-G wherein L 2 and L 3 are each selected from null and the group consisting of::linear, cyclic or branched C 1, C 2, C 3, C 4, C 5, C 6, C 7, C 8, C 9, C 10, C 11, C 12, C 13 or C 14, alkyl or hetero-alkyl, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, or thiol; or linked to an ether group; linear, cyclic or branched C 2, C 3, C 4, C 5, C 6, C 7, C 8, C 9, C 10, C 11, C 12, C 13 or C 14 alkylene or heteroalkylene, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, thiol; or linked to an ether group; C 5, C 6, C 7, C 8, C 9, C 10, C 11, C 12, C 13 or C 14 aryl or heteroaryl, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, thiol; or linked to an ether group; -(O-CH 2 -CH 2) u -, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, or thiol; nucleoside, nucleotide; imidazole, azide, acetylene; and any combinations thereof, wherein each is optionally substituted by one or more halogen, hydroxyl, methoxy, fluorocarbon, amine, thiol; or linked to an ether group; and wherein u is an integer of 1, 2, 3, 4 or 5; and any combinations thereof; and W and G are each independently selected from null, oxygen, ester, amide or secondary or tertiary amine groups; a, b, k and d each stands independently for integer of 0, 1, 2, 3, 4, 5 or 6; R', R", R′′′ and R IV are each selected from the group consisting of hydrogen, methyl and ethyl; and U is selected from the group consisting of null, -O-, ester, amide, and amine (secondary or tertiary amine).